Protein Family Models

The AmpG family muropeptide MFS transporter is a member of the major facilitator superfamily (MFS) involved in the transport of muropeptides across the cell membrane. This family includes proteins such as the anhydromuropeptide permease (AmpG) found in Escherichia coli (strain K12 and O157:H7), which plays a crucial role in cell wall peptidoglycan recycling by transporting disaccharides and peptides from the periplasm into the cytoplasm. The transport process is dependent on the proton motive force. AmpG is also implicated in beta-lactamase induction. Note that this model was rebuilt in 2024, and no longer includes eukaryotic acetyl-coenzyme A transporters within its scope.

Date:

2024-09-25

This HMM describes coenzyme PQQ biosynthesis protein B, a gene required for the biosynthesis of pyrrolo-quinoline-quinone (coenzyme PQQ). PQQ is required for some glucose dehydrogenases and alcohol dehydrogenases. Note that this gene appears to be required for PQQ in biosynthesis in Methylobacterium extorquens (under the name pqqG) and in Klebiella pneumoniae but that the equivalent pqqV in Acinetobacter calcoaceticus is not necessary for heterologous expression of PQQ biosynthesis in E. coli. Based on this latter finding, it is suggested (Goosen, et al. 1989) that PqqB might be a transporter or a PQQ-dependent enzyme rather than a PQQ biosynthesis enzyme.

Gene:

pqqB

Date:

2024-08-23

hybrid SDR (short-chain dehydrogenase/reductase) family oxidoreductase/bifunctional coenzyme A synthase with RNA polymerase Rpb5 N-terminal domain

Date:

2024-02-09

NADH:ubiquinone oxidoreductase subunit NDUFA12 is part of the complex that catalyzes the transfer of electrons from NADH to coenzyme Q10 (CoQ10)

Date:

2024-02-09

Members of this family are involved in quorum sensing processes. In gram negative bacteria, N-acylhomoserine lactones (AHLs) act as signals. As the bacterial density increases, AHLs accumulate, and once they reach a critical level (quorum), they interact with cognate receptor proteins, which then affect target gene expression. Some AHLs are synthesized by LuxM (AHL synthase) and homologs (VanM and opaM)[1]. LuxM enzymes use S-adenosyl-methionine (SAM) as one of its two substrates and are capable of using either acyl-acyl-carrier-protein (acyl-ACP) or acyl-coenzyme A (acyl-CoA) as the other substrate [2]. VanM, the LuxM homolog, produces two auto-inducers C6HSL and 3OC6HSL. Both autoinducers are detected by the VanN receptor. The autoinducers HAI-1, is synthesized by the cytoplasmic enzymes LuxM [3]. [1]. 26655754. A New N-Acyl Homoserine Lactone Synthase in an Uncultured. Symbiont of the Red Sea Sponge Theonella swinhoei.. Britstein M, Devescovi G, Handley KM, Malik A, Haber M, Saurav. K, Teta R, Costantino V, Burgsdorf I, Gilbert JA, Sher N,. Venturi V, Steindler L;. Appl Environ Microbiol. 2015;82:1274-1285.. [2]. 22825856. Quorum sensing: how bacteria can coordinate activity and. synchronize their response to external signals?.. Li Z, Nair SK;. Protein Sci. 2012;21:1403-1417.. [3]. 19686078. Bacterial quorum-sensing network architectures.. Ng WL, Bassler BL;. Annu Rev Genet. 2009;43:197-222. (from Pfam)

Date:

2024-08-14

This is the dimerization domain (DD) found in Yos9 proteins in yeast. Structural analysis revealed that this domain contributes to self association of Yos9. The overall fold of the domain can be classified as an alpha-beta-roll architecture, comprising two alpha-helices and seven beta-strands [1]. [1]. 22262864. Structural and biochemical basis of Yos9 protein dimerization. and possible contribution to self-association of. 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation. ubiquitin-ligase complex.. Hanna J, Schutz A, Zimmermann F, Behlke J, Sommer T, Heinemann. U;. J Biol Chem. 2012;287:8633-8640. (from Pfam)

Date:

2024-08-14

This is the alpha helical domain of ribonucleotide reductases. Family members include Ribonucleotide reductase (RNR, EC:1.17.4.1) [1, 2] which catalyse the reductive synthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. This domain is found in Class II. Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Many organisms have more than one class of RNR present in their genomes. Ribonucleotide reductase is an oligomeric enzyme composed of a large sub-unit (700 to 1000 residues) and a small sub-unit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain [3]. Some family members carry ATP cone domain which acts as a functional regulator. Competitive binding of ATP and dATP to an N-terminal ATP-cone domain determines enzyme activity. As the ratio of dATP to ATP increases above a certain threshold, the enzyme activity is turned off. Substrate nucleotides are recognised by relatively simple H-bonding interactions at the N-terminus of one or more alpha helices. In the monomeric class II RNR, the effector binds in a pocket formed by helices in a 130 amino acid insertion which constitutes this domain [4]. [1]. 3286319. Structure-function studies of the large subunit of. ribonucleotide reductase from Escherichia coli.. Nilsson O, Lundqvist T, Hahne S, Sjoberg BM;. Biochem Soc Trans. 1988;16:91-94.. [2]. 8511586. From RNA to DNA, why so many ribonucleotide reductas. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

This family represents the BT domain in the methylcrotonoyl-CoA carboxylase subunit alpha, located between the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains. This domain mediates crucial interactions between the BC domain in the the alpha subunit and the carboxyltransferase (CT) domain in the beta subunit of this enzyme which are based on ion-pair, hydrogen-bonding and hydrophobic interactions. This domain has a backbone fold with a long helix surrounded by an eight-stranded anti-parallel beta barrel. There is a hook comprising the C-terminal part of the helix and the loop connecting it to the first strand of the beta barrel, which appears to have a central role in alpha and beta subunits interactions [1,2,3]. [1]. 22869039. Structure and function of biotin-dependent carboxylases.. Tong L;. Cell Mol Life Sci. 2013;70:863-891.. [2]. 22158123. An unanticipated architecture of the 750-kDa alpha6beta6. holoenzyme of 3-methylcrotonyl-CoA carboxylase.. Huang CS, Ge P, Zhou ZH, Tong L;. Nature. 2011;481:219-223.. [3]. 20725044. Crystal structure of the alpha(6)beta(6) holoenzyme of. propionyl-coenzyme A carboxylase.. Huang CS, Sadre-Bazzaz K, Shen Y, Deng B, Zhou ZH, Tong L;. Nature. 2010;466:1001-1005. (from Pfam)

Date:

2024-08-14

Acetyl-coenzyme A (CoA) synthase/carbon monoxide dehydrogenase (ACS/CODH) is a bifunctional enzyme that catalyzes the reversible reduction of CO2 to CO (CODH activity). This entry is for the N-terminal domain found in ACS/CODH subunit alpha [1]. [1]. 12627225. Ni-Zn-[Fe4-S4] and Ni-Ni-[Fe4-S4] clusters in closed and open. subunits of acetyl-CoA synthase/carbon monoxide dehydrogenase.. Darnault C, Volbeda A, Kim EJ, Legrand P, Vernede X, Lindahl PA,. Fontecilla-Camps JC;. Nat Struct Biol. 2003;10:271-279. (from Pfam)

Date:

2024-08-14

AdoCbl-dependent diol dehydratase (DD) (EC 4.2.1.28) is one of the enzymes that catalyzes the conversion of 1,2-propanediol, 1,2-ethanediol, and glycerol to the corresponding aldehydes. A DD-reactivating factor (DDR) is responsible for the rapid reactivation of the inactivated holoDD in the presence of AdoCbl, ATP, and Mg2+. DDR exists as a dimer of heterodimer (alpha-beta)2. The alpha subunit has four domains: ATPase domain, swiveling domain, linker domain, and insert domain. The beta subunit, composed of a single domain, has a similar fold to the beta subunit of diol dehydratase (DD). This entry describes the swiveling domain of DDR, which structurally connects the beta subunit and the ATPase domain of the other alpha subunit. Furthermore, the beta subunit moves with the swiveling domain while the linker domain acts as a flat spring or a hinge for the domain movement of the swiveling domain [1]. [1]. 16338403. Release of a damaged cofactor from a coenzyme B12-dependent. enzyme: X-ray structures of diol dehydratase-reactivating. factor.. Shibata N, Mori K, Hieda N, Higuchi Y, Yamanishi M, Toraya T;. Structure. 2005;13:1745-1754. (from Pfam)

Date:

2024-08-14

This domain is found in thiolase-like protein type 1 (TLP1) present in Mycobacterium smegmatis. Thiolase enzymes are acetyl-coenzyme A acetyltransferases which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. This domain is deemed an additional C-terminal region, much like the SPC2-thiolase present in mammals which has an additional C-terminal domain termed the sterol carrier protein-2 (SPC2). However, the additional C-terminal domain in TLP1 folds differently to the traditional SCP2-fold observed in mammalian SPC2-thiolase. The topology of the C-terminal domain of TLP1 is reminiscent of single strand nucleic acid binding proteins [1]. [1]. 22844533. Crystal structure of a monomeric thiolase-like protein type 1. (TLP1) from Mycobacterium smegmatis.. Janardan N, Harijan RK, Wierenga RK, Murthy MR;. PLoS One. 2012;7:e41894. (from Pfam)

Date:

2024-08-14

Capsular polysaccharides (CPSs) are protective structures on the surfaces of many Gram-negative bacteria. wcbI is one of several genes in the CPS biosynthetic cluster whose deletion leads to significant attenuation of the pathogen. Structural analysis and biophysical assays suggest that WcbI functions as an acetyltransferase enzyme but it requires another functional module to carry out this function. WcbI adopts a predominantly helical fold where the N-terminal 100 amino acids form a ligand-binding domain and binds tightly to coenzyme A and its derivative acetyl-CoA [1]. [1]. 25075317. Structural insights into WcbI, a novel. polysaccharide-biosynthesis enzyme.. Vivoli M, Ayres E, Beaumont E, Isupov MN, Harmer NJ;. IUCrJ. 2013;1:28-38. (from Pfam)

Date:

2024-08-14

This family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from mycobacteria [1]. The structure for this domain is known to be a TIM barrel. Both MTHFR1 and MTHFR2 found in Mycobacterium smegmatis are involved in de novo methionine biosynthesis and required for antifolate resistance in mycobacteria [1]. Both of these MTHFRs are monomeric and lack flavin coenzymes [1]. [1]. 32253341. Monomeric NADH-Oxidizing Methylenetetrahydrofolate Reductases. from Mycobacterium smegmatis Lack Flavin Coenzyme.. Sah S, Lahry K, Talwar C, Singh S, Varshney U;. J Bacteriol. 2020; [Epub ahead of print] (from Pfam)

Date:

2024-08-14

This domain is found in Propionyl-coenzyme A carboxylase (PCC), present in Roseobacter denitrificans. PCC is a mitochondrial biotin-dependent enzyme that is essential for the catabolism of certain amino acids, cholesterol, and fatty acids with an odd number of carbon atoms. Since this domain mediates biotin carboxylase-carboxyltransferase interactions it is referred to as the BT domain. The BT domain is located between biotin carboxylase and the biotin carboxyl carrier protein domains. The BT domain shares some structural similarity with the pyruvate carboxylase tetramerization domain of pyruvate carboxylase [1]. [1]. 20725044. Crystal structure of the alpha(6)beta(6) holoenzyme of. propionyl-coenzyme A carboxylase.. Huang CS, Sadre-Bazzaz K, Shen Y, Deng B, Zhou ZH, Tong L;. Nature. 2010;466:1001-1005. (from Pfam)

Date:

2024-08-14

This entry is for the pleckstrin homology-like (PHL) subdomain found in Jak1 proteins. JAK1 is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases that are activated in response to cytokines and interferons. PHL (residues 283-419) together with the N-terminal ubiquitin-like subdomain (residues 36-111) and an acyl-coenzyme A binding protein-like subdomain (residues 148-282), associate into a canonical tri-lobed FERM domain [1]. [1]. 27133025. The Structural Basis for Class II Cytokine Receptor Recognition. by JAK1.. Ferrao R, Wallweber HJ, Ho H, Tam C, Franke Y, Quinn J, Lupardus. PJ;. Structure. 2016;24:897-905. (from Pfam)

Date:

2024-08-14

This is the C-terminal domain secreted by Mycobacterium tuberculosis (Mtb). It induces necrosis of infected cells to evade immune responses. Mtb utilizes the protein CpnT to kill human macrophages by secreting its C-terminal domain (CTD), named tuberculosis necrotizing toxin (TNT) that induces necrosis. It acts as a NAD+ glycohydrolase which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol of infected macrophages resulting in necrotic cell death [1]. CpnT transports its toxic CTD from the cell surface of M. tuberculosis by proteolytic cleavage, where the toxin is cleaved to induce host cell death [2]. Structural analysis determined that the TNT core contains only six beta-strands as opposed to seven found in all known NAD+-utilizing toxins, and is significantly smaller, with only two short alpha-helices and two 3/10 helices. Furthermore, the putative NAD+ binding pocket identified Q822, Y765 and R757 as residues possibly involved in NAD+-binding and hydrolysis based on similar positions of catalytic amino acids of ADP-ribosylating toxins. While glutamine 822 residue was detected to be highly conserved among TNT homologs [1]. [1]. 26237511. The tuberculosis necrotizing toxin kills macrophages by. hydrolyzing NAD.. Sun J, Siroy A, Lokareddy RK, Speer A, Doornbos KS, Cingolani G,. Niederweis M;. Nat Struct Mol Biol. 2015;22:672-678.. [2]. 24753609. An outer membrane channel protein of Mycobacterium tuberculosis. with exotoxin activity.. Danilchanka O, Sun J, Pavlenok M, Maueroder C, Speer A, Siroy A,. Marrero J, Trujillo C, Mayhew DL, Doornbos KS, Munoz LE,. Herrmann M, Ehrt S, Berens C, Niederweis M;. Proc Natl. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-08-14

This small family includes, GlmL/MutL from Clostridium tetanomorphum and Clostridium cochlearium. GlmL is located between the genes for the two subunits, epsilon (GlmE) and sigma (GlmS), of the coenzyme-B12-dependent glutamate mutase (methylaspartate mutase), the first enzyme in a pathway of glutamate fermentation. Members shows significant sequence similarity to the hydantoinase branch of the hydantoinase/oxoprolinase family [2]. [1]. 8428631. Cloning and sequencing of glutamate mutase component E from. Clostridium tetanomorphum. Organization of the mut genes.. Holloway DE, Marsh EN;. FEBS Lett. 1993;317:44-48.. [2]. 7880251. Characterization of the coenzyme-B12-dependent glutamate mutase. from Clostridium cochlearium produced in Escherichia coli.. Zelder O, Beatrix B, Leutbecher U, Buckel W;. Eur J Biochem. 1994;226:577-585. (from Pfam)

Date:

2024-08-14

This domain may well interact selectively and non-covalently with ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. (from Pfam)

Date:

2024-08-14

This domain is found at the N-terminus of many acetyl-coenzyme A synthetase enzymes. (from Pfam)

Date:

2024-08-14

Acyl-coenzyme A oxidase consists of three domains. An N-terminal alpha-helical domain, a beta sheet domain (Pfam:PF02770) and a C-terminal catalytic domain (Pfam:PF01756). This entry represents the N-terminal alpha-helical domain [1]. [1]. 15581893. Acyl-CoA oxidase 1 from Arabidopsis thaliana. Structure of a key. enzyme in plant lipid metabolism.. Pedersen L, Henriksen A;. J Mol Biol. 2005;345:487-500. (from Pfam)

Date:

2024-08-14