Table S2: Functional and spatial relationships between domains of some of the over-represented supra-domains shared by bacteria, archaea and eukaryotes

These 116 supra-domains have a homologue of known structure, and a representative PDB chain identifier is given for each supra-domain. In some cases this particular structure is used to illustrate the function, while in other cases the description applies to all proteins of known structure with those domains.

PDB e.g.

Combination

SF

Function

SF

Function

Functional relationship

Spatial relationship

 

75 Complex Supra-Domains

1af7_

a.58.1.-c.66.1.

Chemotaxis receptor methyltransferase CheR, N-terminal domain (a.58.1)

Small contribution to, S-adenosyl-L-methionine, (AdoMet) binding

S-adenosyl-L-methionine-dependent methyltransferases (c.66.1)

Binds AdoMet, Catalytic domain

Joint activities as substrate is bound by both domains

Interface

1ex1a

c.1.8.-c.23.11.

(Trans)glycosidases (c.1.8)

Active / binding site in cleft between two domains

Beta-D-glucan exohydrolase, C-terminal domain (c.23.11)

Active / binding site in cleft between two domains / putative raw starch binding

Joint activities as binding site between domains

Interface

1b37a

c.3.1.-d.16.1.

FAD/NAD(P)-binding domain (c.3.1)

Catalytic tunnel at domain interface. FAD binding

FAD-linked reductases, C-terminal domain (d.16.1)

Catalytic tunnel at domain interface. Spermidine and spermine binding

Separate activities, but linked by tunnel that imposes constraint on interface

Interface

1aa8a

c.4.1.-d.16.1.

Nucleotide-binding domain (c.4.1)

FAD binding. Active site formed between two domains

FAD-linked reductases, C-terminal domain (d.16.1)

Interface domain binds other interface domain in dimer. Active site formed between two domains

Joint activities as active site formed between domains

Interface

1bfda

c.36.1.-c.31.1.

Thiamin diphosphate-binding fold (THDP-binding) (c.36.1)

Binds Mg2+, Ca2+ and ThDP. Domain makes contacts to thiamine-diphosphate (ThDP) cofactor bound between two dimers and makes dimer contacts. All domains contribute to active site and substrate binding in between dimers

DHS-like NAD/FAD-binding domain (c.31.1)

Space filler. Makes tetramer contacts / oligomerisation domain. All domains contribute to active site and substrate binding in between dimers

Joint activities.

Interface

1c47a

c.84.1.-d.129.2.

Phosphoglucomutase, first 3 domains (c.84.1)

Active site formed in between domains via C-terminal ends of beta sheets of all domains. Both domains involved in oligomerisation

Phosphoglucomutase, C-terminal domain (d.129.2)

Active site formed in between domains via C-terminal ends of beta sheets of all domains. Both domains involved in oligomerisation

Joint activities

Interface

1fwka

d.14.1.-d.58.26.

Ribosomal protein S5 domain 2-like (d.14.1)

Binds ATP, both domains contribute to homoserine binding and active site

GHMP Kinase (d.58.26)

Dimerisation interface present on face helix and sheet. Both domains contribute to active site and homoserine binding

Joint activities

Interface

1a2va

d.17.2.-b.30.2.

Copper amine oxidase, domains 1 and 2 (d.17.2)

Forms channel to active site.

Copper amine oxidase, domain 3 (catalytic) (b.30.2)

Active site. Binds Copper and co-factor TPQ. Oligomerisation interface

Separate activities, linked via channel.

Interface

1ct9a

d.153.1.-c.26.2.

N-terminal nucleophile aminohydrolases (Ntn hydrolases) (d.153.1)

Has active site responsible for hydrolysis of glutamine. Both active sites are joined by a tunnel. Both domains make dimer contacts

Adenine nucleotide alpha hydrolases (c.26.2)

Second active site. Responsible for binding Mg2+ATP and aspartate. Both active sites are joined by a tunnel. Both domains make dimer contacts

Separate activities, but channel between them constrains interface

Interface

1ao0a

d.153.1.-c.61.1.

N-terminal nucleophile aminohydrolases (Ntn hydrolases) (d.153.1)

Glutamine binding. Both domains contact themselves in tetramer

PRTase-like (c.61.1)

4Fe-4S binding. Binds AMP in catalytic and regulatory sites. Both domains contact themselves in tetramer

Separate activites, but cooperate to catalyse transfer of ammonia.

Interface

1e5da

d.157.1.-c.23.5.

Metallo-hydrolase/oxidoreductase (d.157.1)

Catalytic domain Fe 2 centre. Binds dioxygen

Flavoproteins (c.23.5)

Binds FMN co-factor. Dimerisation domain

Separate activities, but cooperate to catalyse reaction.

Interface

1jnra

c.3.1.-d.168.1.

FAD/NAD(P)-binding domain

Binds FAD

Succinate dehydrogenase/fumarate reductase, catalytic domain

Binds succinate. Active site formed in cavity between two domains.

The NTD is actually discontinuous, with the CTD inserted inside. The CTD is observed in combination with the NTD only – its a rare domain that is found only in these oxidoreductases acting on dicarboxylic substrates (Bossi et al., 2002).

Interface

1abma

a.2.11.-d.44.1.

Fe,Mn superoxide dismutase (SOD), N-terminal domain

Both domains contribute to catalytic manganese site as well as provide interactions for oligomerisation

Fe,Mn superoxide dismutase (SOD), C-terminal domain

Both domains contribute to catalytic manganese site as well as provide interactions for oligomerisation

Both domains contribute to catalytic manganese site as well as provide interactions for oligomerisation

Interface

1a71a

b.35.1.-c.2.1.

GroES-like

Catalytic domain, alcohol binding, bind two Zinc ions one of which is catalytic

NAD(P)-binding Rossmann-fold domains

NAD+ binding, dimerisation domain

Though the two domains bind distinct molecules, the two molecules have to be positioned carefully for the reaction to be catalysed, so the function is effectively joint

Interface

1bg6_

c.2.1.-a.100.1.

NAD(P)-binding Rossmann-fold domains

NAD+ binding

6-phosphogluconate dehydrogenase C-terminal domain-like

Catalytic domain, N-(1-D-carboxylethyl)-L-norvaline binding, also acts as a dimerisation

Though the two domains bind distinct molecules, the two molecules have to be positioned carefully for the reaction to be catalysed, so the function is effectively joint

Interface

1cqia

c.2.1.-c.23.4.

NAD(P)-binding Rossmann-fold domains

CoA binding

Succinyl-CoA synthetase domains

Catalytic domain, Succinate binding

 

"

Interface

1a7ka

c.2.1.-d.81.1.

NAD(P)-binding Rossmann-fold domains

NAD+ binding

Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain

Catalytic domain, Glyceradehyde-3-phospate binding

 

"

Interface

1a7aa

c.23.12.-c.2.1.

Formate/glycerate dehydrogenase catalytic domain-like

Catalytic domain, binds substrate S-adenosylhomocystein. Both domains make contacts to other chains in the tetramer

NAD(P)-binding Rossmann-fold domains

NAD+ binding. Both domains make contacts to other chains in the tetramer

 

"

Interface

1aoga

c.3.1.-d.87.1.

FAD/NAD(P)-binding domain

FAD binding, binds trypanothione with C-terminal domain from other chain in dimer in trypanothione reductase. Contributes residues to the active site and forms dimer contacts.

FAD/NAD-linked reductases, dimerisation (C-terminal) domain

Interface domain, important dimer contacts. Binds trypanothione with other domain in trypanothione reductase.

The function is joint between the two domains, but some interactions are across domains in multimeric proteins with these domains

Interface

1gsa_

c.30.1.-d.142.1.

Biotin carboxylase N-terminal domain-like

Both domains contribute to active site and GSH binding in glutathione synthetase

Glutathione synthetase ATP-binding domain-like

Binds ADP. Both domains contribute to active site and GSH binding in glutathione synthetase

The active site is formed jointly by both domains

Interface

1a4ia

c.58.1.-c.2.1.

Aminoacid dehydrogenase-like, N-terminal domain

Catalytic domain, tetrahydrofolate binding in tetrahydrofolate dehydrogenase/cyclohydrolase, both domains make dimer contacts

NAD(P)-binding Rossmann-fold domains

NADP+ binding, both domains make dimer contacts

Though the two domains bind distinct molecules, the two molecules have to be positioned carefully for the reaction to be catalysed, so the function is effectively joint

Interface

1fgs_

c.72.2.-c.59.1.

MurD-like peptide ligases, catalytic domain

Active site between two domains. ATP and folate bound between two domains in folypolyglutamate synthase

MurD-like peptide ligases, peptide-binding domain

Active site between two domains. ATP and folate bound between two domains domains in folypolyglutamate synthase

The active site is formed jointly by both domains

Interface

1a9xb

c.8.3.-c.23.16.

Carbamoyl phosphate synthetase, small subunit N-terminal domain

Substrate Gln bound between domains in carbamoyl phosphate synthase

Class I glutamine amidotransferase-like

Active site residues. Substrate Gln bound between domains in carbamoyl phosphate synthase

 

"

Interface

1aco_

c.83.1.-c.8.2.

Aconitase, first 3 domains

Binds 4Fe-4S cluster. All four domains contribute residues to active site in aconitase.

Aconitase, C-terminal domain

All four domains contribute residues to active site in aconitase

 

"

Interface

1ahva

d.145.1.-d.58.32.

FAD-binding domain

FAD binding. Both domains contribute residues to the active site.

FAD-linked oxidases, C-terminal domain

Binds FAD. Cap domain covers active site. Both domains contribute residues to the active site. Binds substrate.

The active site is formed jointly by both domains

Interface

1f52a

d.15.9.-d.128.1.

Glutamine synthetase, N-terminal domain

Both domains contribute beta strands to active site and substrate binding. The active site is formed with an adjacent subunit in glutamine synthase.

Glutamine synthase/guanidino kinase catalytic domain

Both domains contribute beta stands to active site and substrate binging. The active site is formed with an adjacent subunit. Binds ATP and 2Mg2+. Also regulatory functions in glutamine synthase.

The active site is formed jointly by both domains

Interface

1ush_

d.159.1.-d.114.1.

Metallo-dependent phosphatases

2Zn2+ binding. Active site in this domain.

5'-nucleotidase (syn. UDP-sugar hydrolase), C-terminal domain

Substrate-binding domain.

The two domains have separate functions, but the interface is important for catalytic activity in the sense that the substrate must be positioned relative to the active site.

Interface

1clia

d.79.4.-d.139.1.

Aminoimidazole ribonucleotide synthetase (PurM) N-terminal domain

Dimerisation domain. Active site formed between domains and with one domain on other subunit of multimer. Sulphate ion bound between domains

Aminoimidazole ribonucleotide synthetase (PurM) C-terminal domain

Active site formed between domains and domain X other monomer. Sulphate ion bound between and involved in active site

The active site is formed jointly by both domains

Interface

1jxaa

d.153.1.-c.80.1.

N-terminal nucleophile aminohydrolases (Ntn hydrolases)

Catalyses hydrolysis of glutamine to glutamate for instance in glucosamine-6-phosphate synthase (Teplyakov et al., 2001)

SIS domain

Sugar isomerase domain

The two domains have separate functions, but are connected by a small interface that contains a channel for ammonia in glucosamine-6-phosphate synthase. Thus the interface is of a special character, and is conserved throughout the reaction, though there is motion within the SIS domain.

Interface

1b6ra

d.142.1.-b.84.2.

Glutathione synthetase ATP-binding domain-like

ATP-binding

Rudiment single hybrid motif

Major substrates bound by combination of both domains (Thoden et al., 1999)

Interface

1buca

e.6.1.-a.29.3.

Acyl-CoA dehydrogenase NM domain-like

A binding pocket for FAD and acyl-CoA is formed at the interface of the two domains (Battaile et al., 2002).

Acyl-CoA dehydrogenase C-terminal domain-like

A binding pocket for FAD and acyl-CoA is formed at the interface of the two domains (Battaile et al., 2002).

Many of the enzymes containing this supra-domain are involved in oxidation of fatty acids and amino acid catabolism.

Interface

1a8p_

b.43.4.-c.25.1.

Riboflavin synthase domain-like

Binds FAD

Ferredoxin reductase-like, C-terminal NADP-linked domain

Binds NADPH

Electron transfer takes place between two cofactors, so domains are precisely placed relative to each other. Used in conjunction with other domains to oxidize/reduce various substrates (Ingelman et al., 1997)

Interface

1h19a

b.98.1.-d.92.1.

Leukotriene A4 hydrolase N-terminal domain

The N-terminal domain combines with the catalytic domain to form the substrate-binding pocket.

Metalloproteases ("zincins"), catalytic domain

The catalytic domain harbours a catalytic Zn2+ site that can be used for peptidase reactions, but also epoxide hydrolase activity in combination with other catalytic residues in leukotriene A4 hydrolase (Thunnissen et al., 2001).

Interface

1qapa

d.41.2.-c.1.17.

Quinolinic acid phosphoribosyltransferase, N-terminal domain

Shields active site from solvent. Contributes to active site in other monomer in QAPRTase

Quinolinic acid phosphoribosyltransferase, C-terminal domain

Catalytic domain. Binds NAMN in QAPRTase

The active site is formed jointly by both domains, but across chains of homomultimer in QPRTase for instance

Interface across chains, but separate within chain

1e3pa

d.14.1.-d.101.1.

Ribosomal protein S5 domain 2-like

There are two copies of this domain in PNPase, and one copy in Rnase P. In PNPase, it forms the trimerization interface, and it is likely that this domain binds Pi. It is also likely that it bind RNA.

Polynucleotide phosphorylase/guanosine pentaphosphate synthase (PNPase/GPSI), domains 2 and 5

This domain forms intramolecular homodimer interface, also makes trimerization contacts and probably binds RNA. In the GPSI activity of PNPase, it may bind pppGpp.

The NTD occurs in lots of different types of proteins (kinases – see below, DNA gyrase, translation machinery etc.)

Combination occurs in many different types of domain architectures. In PNPase, there are two copies of this supra-domain, and these two copies trimerize. Reaction mechanisms and active site are not fully known.

Ribosomal protein domain is NTD for most small molecule kinases, but CTD in supra-domain below.

Most probably interface, though catalytic mechanism is unknown for either PNPase or GPSI (Symmons et al., 2003)

1aop_

d.58.36.-d.134.1.

Sulfite reductase, domains 1 and 3 (d.58.36)

Binds substrate (sulfite) and contacts siroheam. Enzyme has active centre that is formed between two copies of this domain.

Sulfite reductase hemoprotein (SiRHP), domains 2 and 4 (d.134.1)

Binds sirohaem cofactor and 4Fe-2S centre.

Linked activities

Probably interface

1eh6a

c.55.7.-a.4.2.

Methylated DNA-protein cysteine methyltransferase domain (c.55.7)

Contacts ‘Asn-hinge’ in inter-domain interface

Methylated DNA-protein cysteine methyltransferase, C-terminal domain (a.4.2)

Active site Cysteine O6-alkylguanine-binding channel. HTH DNA binding motif

N-terminal domain does not have known function, but is implicated in protein stability and motion

Probably separate

1a0i_

d.142.2.-b.40.4.

DNA ligase/mRNA capping enzyme, catalytic domain (d.142.2)

DNA / ATP binding / Enzyme Active site

Nucleic acid-binding proteins (b.40.4)

Forms DNA binding cleft with N-terminal domain

Unclear, but partially joint activities through DNA-binding.

Probably separate as it is likely that there is domain motion, and relative positions of domains vary in different structures

1ffh_

a.24.13.-c.37.1.

Domain of the SRP/SRP receptor G-proteins

A 4- helix bundle that is an extension of the GTPase domain. Present in both FfH and FtsY. May be involved in mediating signal peptide binding from M domain by conformational change, and interaction with ribosome.

P-loop containing nucleotide triphosphate hydrolases

GTPase domain, might be involved in SRP/receptor interaction through homologous domain in SR. Hydrolysis of GTP leads to release from receptor.

This supra-domain occurs both in the SRP and its receptor. The system is conserved in eukaryotes and all prokaryotes, though other elements of SRP vary (Nagai et al., 2003; Montoya et al,. 2000)

Most probably separate, though the NTD function is not entirely characterised.

1cf9a

e.5.1.-c.23.16.

Heme-linked catalases (e.5.1)

Catalytic domain; heme binding. Both domains involved in tetramer formation

Class I glutamine amidotransferase-like (c.23.16)

Unknown. Both domains involved in tetramer formation

Role of C-teminal domain is unclear, except that it is involved in tetramer formation

Probably separate

1dfaa

b.86.1.-d.95.2.

Hedgehog/intein (Hint) domain (b.86.1)

Protein splicing domain

Homing endonucleases (d.95.2)

Endonuclease and DNA binding domain

Separate activities

Separate

1aa6_

c.81.1.-b.52.2.

Formate dehydrogenase/DMSO reductase, domains 1-3 (c.81.1)

Binds MGD (co-factor). Fe4S4 cluster. Active site

ADC-like (b.52.2)

Forms cap on enzyme over co-factors

Activities of domains are cooperative, but involve domain motion.

Separate

1acmb

d.58.2.-g.41.7.

Aspartate carbamoyltransferase, Regulatory-chain, N-terminal domain (d.58.2)

Allosteric domain with CTP binding site. Dimerisation domain

Aspartate carbamoyltransferase, Regulatory-chain, C-terminal domain (g.41.7)

Zinc binding domain. Interacts with catalytic chain, zinc necessary for interaction. Zinc does not have a catalytic role.

Separate activities, with protein motion between domains and chains

Separate

1ar1b

f.17.2-b.6.1.

Cytochrome c oxidase subunit II-like, transmembrane region (f.17.2.)

Transmembrane region. Interacts with subunit I to form complex in membrane region

Cupredoxins (b.6.1)

Contains 2Cu2 centre which acts as an acceptor of electrons from reduced cytochrome c

Part of larger complex.

Separate

1fsz_

c.32.1.-d.79.2.

Tubulin, GTPase domain

GTPase domain. Binds GTP

Tubulin, C-terminal domain

Interacts with ZipA in FtsZ. Protein-protein interaction domain

The functions of the two domains are distinct.

Separate

1a8h_

c.26.1.-a.27.1.

Nucleotidylyl transferase

Catalytic / amino acid binding.

Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases

Anticodon binding domain

The activities of the two domains are clearly defined and distinct

Separate

1euqa

c.26.1.-b.53.1.

Nucleotidylyl transferase

Catalytic / amino acid binding.

Ribosomal protein L25-like

Anticodon binding

There is protein motion between the two domains during catalysis

Separate

1blle

c.50.1.-c.56.5.

Leucine aminopeptidase, N-terminal domain

Mediates trimer-trimer interactions in leucine aminopeptidase

Zn-dependent exopeptidases

Catalytic domain, Zn2+ binding

The functions of the two domains are distinct

Separate

1a16_

c.55.2.-d.127.1.

Creatinase/prolidase N-terminal domain

Oligomerisation domain

Creatinase/aminopeptidase

Active site with 2Mg2+ centre. Oligomerisation. Contributes to active site in neighbouring subunit

The two domains make separate multimeric contact and so are functionally entirely distinct

Separate

1d5aa

c.55.3.-e.8.1.

Ribonuclease H-like

Exonuclease proof reading domain

DNA/RNA polymerases

DNA polymerase domain

The two domains have independent functions

Separate

1cg2a

c.56.5.-d.58.19.

Zn-dependent exopeptidases

Catalytic domain, Zn2+ binding

Carboxypeptidase G2, dimerisation domain

Dimerisation domain

 

"

Separate

1hv9a

c.68.1.-b.81.1.

Nucleotide-diphospho-sugar transferases

Uridyl transferase domain. Catalyses the formation of UDP-GlcNAc and pyrophosphate from GlcNAc-1-PO4 and UTP in N-acetylglucosamine-1-P04-uridyltransferase

Trimeric LpxA-like enzymes

Acetyltransferase domain. Active site formed by residues from all 3 chains of the trimer. Catalyses the CoA dependent acylation of Glc-1-PO4 in in N-acetylglucosamine-1-P04-uridyltransferase

The two domains have independent functions

Separate

1adja

d.104.1.-c.51.1.

Class II aaRS and biotin synthetases

Catalytic domain

Anticodon-binding domain of Class II aaRS

Anticodon binding domain

Protein motion between domains upon catalysis

Separate

1bkha

d.54.1.-c.1.11.

Enolase N-terminal domain-like

Involved in oligomerisation

Enolase C-terminal domain-like

Catalytic domain with active site and manganese ion

The functions of the two domains are distinct

Separate

1ky9a

b.47.1.-b.36.1.

Trypsin-like serine proteases

Proteolysis

PDZ domain-like

Oligomerisation, possibly substrate binding, substrate recruitment and regulation of protease activity.

Mechanism is not entirely clear, but protein motion is involved in these large, trimeric or hexameric proteases (Krojer et al., 2002; Li et al., 2002)

Separate

1b7yb

a.6.1.-d.104.1.

Putative DNA-binding domain

The N-terminal domain is involved in heterodimeric interactions,

binds ATP and the amino acid to catalyze aminoacyl-adenylate formation.

Class II aaRS and biotin synthetases

This domain forms the

homodimeric interface as well as some heterodimeric interactions with the a chain.

This supradomain is in b chain of PheRS, a chain that binds tRNA but is not catalytically active. (The activity resides in the a chain.) The C-terminal domain is usually the catalytic domain for aminoacyl-tRNA charging in most class IIaaRS, but not in PheRS b chain. The a chain is the catalytically active chain, which contains a homologous domain.

Separate

1brwa

a.46.2.-c.27.1

Nucleoside phosphorylase/phosphoribosyl-transferase N-terminal domain

Same fold as methionine synthase, but superfamily does not appear on own. Homo- dimerisation domain.

Nucleoside phosphorylase/phosphoribosyltransferase catalytic domain

Superfamily does appear on own and without NTD in genomes. This domain binds pyrimidine and phosphate and is catalytic.

NTD occurs with CTD only, and has the function of mediating dimerisation. CTD binds all substrates and carries out catalysis with domain motion. Note: definition of domains in SCOP differs from literature (Pugmire & Ealick, 2002).

Separate

1bpe_

a.60.6.-d.218.1.

DNA polymerase beta, N-terminal domain-like

This is the 8kD N-terminal helical domain that exists in pol beta and terminal deoxynucleotidyltransferase.

It is connected to the fingers by a flexible hinge. It contains a helix-hairpin-helix motif, one of which is in the fingers subdomain too. In pol beta, it binds ssDNA and exihibits deoxyribose phosphate lyase activity, but not in terminal deoxynucleotidyltransferase. It touches the thumb domain of the nucleotidyltransferase and forms a hole through which dNTPs reach the active site.

Nucleotidyltransferase

Nucleotidyltransferase consists of two domains in SCOP1.63 that share catalytic activity between them. The fingers domain is split off as a separate superfamily in SCOP1.63.

Separate

1g8ma

c.24.1.-c.97.2.

Methylglyoxal synthase-like

This domain is more common, and catalyses the second reaction, the final step of a purine biosynthesis pathway: FAICAR to IMP by cyclohydrolysis.

AICAR transformylase domain of bifunctional purine biosynthesis enzyme ATIC

This domain is rare – seen in this enzyme only. It catalyses the transformation of AICAR to FAICAR, a stable intermediate.

Both domains make contacts to homologous domains in the homodimer.

Separate

1e79a

c.37.1.-a.69.1.

P-loop containing nucleotide triphosphate hydrolases

In a subunits of ATP synthase, ADP is converted to ATP. The domains are involved in a/b oligomerisation.

C-terminal domain of alpha and beta subunits of F1 ATP synthase

Domains are involved in a/b oligomerisation. This domain in b subunits contacts the g central stalk, and upon rotation the conformational change is transmitted to the catalytic a subunits.

The CTD is seen only with P-loop in all genome domain combinations.

Separate

1aipa

c.37.1.-b.43.3.

P-loop containing nucleotide triphosphate hydrolases

All proteins with this supra-domain for which information is available (Roll-Mecak et al., 2001; Song et al., 1999) contact the base of the L7/L12 stalk through the N-terminal domain.

Translation proteins

Contacts the shoulder of the small subunit of the ribosome

This supra-domain is in all prokaryotic and eukaryotic translation factors that hydrolyze GTP. GTP hydrolysis drives conformational change in second domain, which is transmitted to ribosomal proteins. Proteins with this domain are prokaryotic Initiation factor 2 and the eukaryotic homologue eIF5B, elongation factors Tu and G, equivalent to eukaryotic EF1A and 2, and prokaryotic Release factor 3 and selenocysteinyl-tRNA specific translation factor

Separate

1b3qa

a.30.2.-d.122.1.

Homodimeric domain of signal transducing histidine kinase

Dimerisation domain

ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase

Histidine kinase domain of the type that occurs in two-component signal transduction pathways.

Most of these proteins have additional N-terminal domains that are frequently involved in small-molecule binding. Some of the proteins also have additional C-terminal domains that are equivalent to components downstream in the signal transduction pathway, such as the CheY receiver domain or the histidine phosphotransfer (HPT) domain. All these proteins are probably involved in signal transduction.

Separate

1lnrg

d.47.1.-a.4.7.

Ribosomal protein L11, N-terminal domain

Putative interaction with elongation factors

Ribosomal protein L11, C-terminal domain

Binds 23S rRNA

The NTD is a molecular switch, that can exist in two conformations: either bound or unbound to 23S rRNA. This is thought to be triggered by elongation factor binding. The CTD is stably bound to the 23S rRNA.

Separate

1b62a

d.122.1.-d.14.1.

ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase

Hydrolyzes ATP – the activity is stimulated by DNA binding.

Ribosomal protein S5 domain 2-like

Binds ssDNA and dsDNA in different mismatch repair proteins.

Both domains occur in several different types of proteins. Together, they occur in DNA gyrase and DNA mismatch repair proteins MutL and PMS2.

Separate

1a0p_

a.60.9.-d.163.1.

lambda integrase-like, N-terminal domain (a.60.9)

Putative contribution to DNA binding

DNA breaking-rejoining enzymes (d.163.1)

Putative DNA binding domain. Contains active site tyrosine

Unknown

Difficult as functional relationships unclear.

1ffuc

d.145.1.-d.87.2.

FAD-binding domain (d.145.1)

FAD binding, contacts CutL (chain B)

CO dehydrogenase flavoprotein C-terminal domain-like (d.87.2)

Shields substrate from solvent, contacts CutS and CutL (chains A and B)

Difficult as part of larger complex

Difficult as part of larger complex

1r1ra

a.98.1.-c.7.1.

R1 subunit of ribonucleotide reductase, N-terminal domain (a.98.1)

Regulatory, Allosteric site binds ATP

PFL-like glycyl radical enzymes (c.7.1)

Catalytic and regulatory. Active site binds GDP; allosteric site binds dTTP. Also dimerisation interface and interactions with R2 subunit

Separate activities

Difficult, as part of larger complex

1ffua

d.15.4.-a.56.1.

2Fe-2S ferredoxin-like (d.15.4)

Binds a class II [2Fe-2S] cluster

CO dehydrogenase ISP C-domain like (a.56.1)

Binds a class I [2Fe-2S] cluster

Separate activities within larger complex

Difficult, as part of larger complex

1a5kc

b.92.1.-c.1.9.

alpha-Subunit of urease, composite domain (b.92.1)

Interacts with beta and gamma subunits in urease, alpha subunit

Metallo-dependent hydrolases (c.1.9)

Catalytic domain, with active site nickel centre. Also putative urea binding site in urease, alpha subunit

Separate activities

Difficult, as part of larger complex.

1r1ra

a.98.1.-c.7.1.

R1 subunit of ribonucleotide reductase, N-terminal domain

Regulatory, allosteric site binds ATP in R1 subunit of ribouncleotide reductase

PFL-like glycyl radical enzymes

Catalytic and regulatory. Active site binds GDP, allosteric site binds dTTP. Also dimerisation interface and interactions with R2 subunit in R1 subunit of ribouncleotide reductase

Unknown

Difficult, as part of larger complex. May be separate, as both are individually allosteric

1amy_

c.1.8.-b.71.1.

(Trans)glycosidases (c.1.8)

Catalytic site / substrate binding / Ca2+

alpha-Amylases, C-terminal beta-sheet domain (b.71.1)

Putative raw starch binding domain in alpha amylase

Separate activities

Unknown

1dnpa

c.28.1.-a.99.1.

N-terminal domain of DNA photolyase

Binds light harvesting co-factor 8-HDF

FAD-binding (C-terminal) domain of DNA photolyase

Binds catalytic co-factor FAD. Exact nature of DNA binding and catalysis unknown

The enzymatic mechanism is unknown

Unknown

1dtwb

c.36.1.-c.48.1.

Thiamin diphosphate-binding fold (THDP-binding)

Binds ThDP cofactor with alpha chain. Binds K+ Makes contacts with beta dimer and alpha dimer in beta chain of Branched-chain alpha-keto acid dehydrogenase

Transketolase C-terminal domain-like

Unknown. Makes contacts with beta dimer and alpha dimer in beta chain of branched chain alpha-keto acid dehydrogenase

The function of the C-terminal domain is unknown

Unknown

1a76_

c.53.1.-a.60.7.

Resolvase-like

Contains active site residues. Binds two metal ions

5' to 3' exonuclease, C-terminal subdomain

Space filler. Sub-domain intertwines with other domain. Function not clear

Function of C-terminal domain unknown.

Unknown

1ffub

d.41.1.-d.133.1.

CO dehydrogenase molybdoprotein N-domain-like

Unknown. Does not bind co-factor.

Molybdemum cofactor-binding domain

Molybdenum cofactor binding domain

Function of one domain unknown

Unknown

 

41 Repetitive Supra-domains

 

3 Nucleic Acid Binding Domains

1fgua

b.40.4.-b.40.4.

Nucleic acid-binding proteins

1a5j_

a.4.1.-a.4.1.

Homeodomain-like

1repC

a.4.5.-a.4.5.

"Winged helix" DNA-binding domain

 

4 Cofactor or minor substrate binding domains

1a1va

c.37.1.-c.37.1.

P-loop containing nucleotide triphosphate hydrolases

3ldh_

c.2.1.-c.2.1.

NAD(P)-binding Rossmann-fold domains

1djna

c.3.1.-c.3.1.

FAD/NAD(P)-binding domain

1atna

c.55.1.

Actin-like ATPase domain

 

21 Enzyme

1boi_

c.46.1.-c.46.1.

Rhodanese/Cell cycle control phosphatase

1a8l_

c.47.1.-c.47.1.

Thioredoxin-like

1a1s_

c.78.1.-c.78.1.

Aspartate/ornithine carbamoyltransferase

1k2yx

c.84.1.-c.84.1.

Phosphoglucomutase, first 3 domains

1afwa

c.95.1.-c.95.1.

Thiolase-like

1cjxa

d.32.1.-d.32.1.

Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase

1c8ua

d.38.1.-d.38.1.

Thioesterase/thiol ester dehydrase-isomerase

1qd1a

d.58.34.-d.58.34.

Formiminotransferase domain of formiminotransferase-cyclodeaminase.

1dj0a

d.58.35.-d.58.35.

Pseudouridine synthase

1f0ia

d.136.1.-d.136.1.

Phospholipase D/nuclease

1bcca

d.185.1.-d.185.1.

LuxS/MPP-like metallohydrolase

1itka

a.93.1.-a.93.1.

Heme-dependent peroxidases

1sqc_

a.102.4.

Terpenoid cylases/Protein prenyltransferases

1jflA

c.78.2.

Aspartate/glutamate racemase

1mowJ

d.95.2.

Homing endonucleases

1qrkB

b.1.5.

Transglutaminase, two C-terminal domains

1ivwA

d.17.2.

Copper amine oxidase, domains 1 and 2

1iylC

d.108.1.

Acyl-CoA N-acyltransferases (Nat)

1m3eA

c.63.1.

CoA transferase

1bwzA

d.21.1.

Diaminopimelate epimerase

1qr0A

d.150.1.

4'-phosphopantetheinyl transferase

2 Cell Adhesion

1epfA

b.1.1

Immunoglobulin

2mfn_

b.1.2

Fibronectin type III

 

11 Other

1as6a

b.6.1.-b.6.1.

Cupredoxins

1ak5_

d.37.1.-d.37.1.

CBS-domain

1tdj_

d.58.18.-d.58.18.

Regulatory domain in the aminoacid metabolism

1c3gA

b.4.1.

HSP40/DnaJ peptide-binding domain

1ovt_

c.94.1.

Periplasmic binding protein-like II

1rl6A

d.141.1.-d.141.1.

Ribosomal protein L6

1ky9B

b.36.1.

PDZ domain-like

1hxqB

d.13.1.

HIT-like

1yua_

g.41.3.-g.41.3.

Zinc beta-ribbon

1h9sA

b.40.6.

MOP-like

1plq_

d.131.1.

DNA clamp