Protein Family Models

This HMM describes a recurring sub-architecture, about 1500 amino acids long, with an SDR (short-chain alcohol reductase) at its C-terminus, in addition to a trio of domains shared by all type I polyketide synthases. While the actual function of member proteins is specific to the natural product made, this model is assigned family type equivalog_domain to elevate its precedence in automated annotation software and prevent the misapplication of even more generic annotation.

Date:

2024-04-14

KAsynt_C_assoc represents the very C-terminus of a subset of proteins from the keto-acyl-synthetase 2 family. It is found in proteins ranging from bacteria to human. (from Pfam)

Date:

2023-12-12

This is the dimerisation element domain found in bacterial modular polyketide synthase ketoreductases [1]. The dimerization element (DE) domain is N-terminal to the KR domain Pfam:PF08659. DE domain is necessary for KR function, presumably because the dimeric DE orients the KR domains for optimal activity within a module [2]. [1]. 23489133. The missing linker: a dimerization motif located within. polyketide synthase modules.. Zheng J, Fage CD, Demeler B, Hoffman DW, Keatinge-Clay AT;. ACS Chem Biol. 2013;8:1263-1270.. [2]. 23755878. Structural studies of an A2-type modular polyketide synthase. ketoreductase reveal features controlling alpha-substituent. stereochemistry.. Zheng J, Piasecki SK, Keatinge-Clay AT;. ACS Chem Biol. 2013;8:1964-1971. (from Pfam)

Date:

2024-04-03

This enzymatic domain is part of bacterial polyketide synthases and catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group [1]. [1]. 23790488. Structural and stereochemical analysis of a modular polyketide. synthase ketoreductase domain required for the generation of a. cis-alkene.. Bonnett SA, Whicher JR, Papireddy K, Florova G, Smith JL,. Reynolds KA;. Chem Biol. 2013;20:772-783. (from Pfam)

Date:

2024-04-03

Polyketide synthase (PKS) catalyzes the biosynthesis of polyketides, which are structurally and functionally diverse natural products in microorganisms and plants [1]. Type I modular PKSs are the large, multifunctional enzymes responsible for the production of a diverse family of structurally rich and often biologically active natural products. The efficiency of acyl transfer at the interfaces of the individual PKS proteins is thought to be governed by helical regions, termed docking domains (dd). Two such N-terminal domains dimerise to form amphipathic parallel alpha-helical coiled coils: dimerisation is essential for protein function [1]. [1]. 12954331. The structure of docking domains in modular polyketide. synthases.. Broadhurst RW, Nietlispach D, Wheatcroft MP, Leadlay PF,. Weissman KJ;. Chem Biol. 2003;10:723-731.. [2]. 26611533. Multimodular type I polyketide synthases in algae evolve by. module duplications and displacement of AT domains in trans.. Shelest E, Heimerl N, Fichtner M, Sasso S;. BMC Genomics. 2015;16:1015.. [3]. 19146481. Structural basis for binding specificity between subclasses of. modular polyketide synthase docking domains.. Buchholz TJ, Geders TW, Bartley FE 3rd, Reynolds KA, Smith JL,. Sherman DH;. ACS Chem Biol. 2009;4:41-52. (from Pfam)

Date:

2024-04-03

This is a family of diverse bacterial polysaccharide biosynthesis proteins including the CapD protein (Swiss:P39853) [1], WalL protein (Swiss:O86159) mannosyl-transferase (Swiss:O05349) [2] and several putative epimerases (e.g. WbiI Swiss:O69130). [1]. 7961465. Sequence analysis and molecular characterization of genes. required for the biosynthesis of type 1 capsular polysaccharide. in Staphylococcus aureus.. Lin WS, Cunneen T, Lee CY;. J Bacteriol 1994;176:7005-7016.. [2]. 9079898. Identification of additional genes required for O-antigen. biosynthesis in Vibrio cholerae O1.. Fallarino A, Mavrangelos C, Stroeher UH, Manning PA;. J Bacteriol 1997;179:2147-2153. (from Pfam)

Date:

2024-04-03

The structure of beta-ketoacyl synthase is similar to that of the thiolase family (Pfam:PF00108) and also chalcone synthase. The active site of beta-ketoacyl synthase is located between the N and C-terminal domains. [1]. 9482715. Crystal structure of beta-ketoacyl-acyl carrier protein synthase. II from E.coli reveals the molecular architecture of condensing. enzymes.. Huang W, Jia J, Edwards P, Dehesh K, Schneider G, Lindqvist Y;. EMBO J 1998;17:1183-1191. (from Pfam)

Date:

2024-04-03

This family of proteins utilise NAD as a cofactor. The proteins in this family use nucleotide-sugar substrates for a variety of chemical reactions. [1]. 9174344. Structural analysis of UDP-sugar binding to UDP-galactose. 4-epimerase from Escherichia coli.. Thoden JB, Hegeman AD, Wesenberg G, Chapeau MC, Frey PA, Holden. HM;. Biochemistry 1997;36:6294-6304. (from Pfam)

Date:

2024-04-03

Thiolase is reported to be structurally related to beta-ketoacyl synthase (Pfam:PF00109), and also chalcone synthase. [1]. 9402066. The 1.8 A crystal structure of the dimeric peroxisomal. 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae:. implications for substrate binding and reaction mechanism.. Mathieu M, Modis Y, Zeelen JP, Engel CK, Abagyan RA, Ahlberg A,. Rasmussen B, Lamzin VS, Kunau WH, Wierenga RK;. J Mol Biol 1997;273:714-728. (from Pfam)

Date:

2024-04-03

This family contains a wide variety of dehydrogenases. [1]. 9735295. The refined crystal structure of Drosophila lebanonensis alcohol. dehydrogenase at 1.9 A resolution.. Benach J, Atrian S, Gonzalez-Duarte R, Ladenstein R;. J Mol Biol 1998;282:383-399.. [2]. 10387002. Structure of tropinone reductase-II complexed with NADP+ and. pseudotropine at 1.9 A resolution: implication for. stereospecific substrate binding and catalysis.. Yamashita A, Kato H, Wakatsuki S, Tomizaki T, Nakatsu T,. Nakajima K, Hashimoto T, Yamada Y, Oda J;. Biochemistry 1999;38:7630-7637. (from Pfam)

Date:

2024-04-03

Peptide synthetases are involved in the non-ribosomal synthesis of peptide antibiotics. Next to the operons encoding these enzymes, in almost all cases, are genes that encode proteins that have similarity to the type II fatty acid thioesterases of vertebrates. There are also modules within the peptide synthetases that also share this similarity. With respect to antibiotic production, thioesterases are required for the addition of the last amino acid to the peptide antibiotic, thereby forming a cyclic antibiotic. Thioesterases (non-integrated) have molecular masses of 25-29 kDa. [1]. 9560421. Genetic evidence for a role of thioesterase domains, integrated. in or associated with peptide synthetases, in non-ribosomal. peptide biosynthesis in Bacillus subtilis.. Schneider A, Marahiel MA;. Arch Microbiol 1998;169:404-410. (from Pfam)

Date:

2024-04-03

A 4'-phosphopantetheine prosthetic group is attached through a serine. This prosthetic group acts as a a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups. This domain forms a four helix bundle. This family includes members not included in Prosite. The inclusion of these members is supported by sequence analysis and functional evidence. The related domain of Swiss:P19828 has the attachment serine replaced by an alanine. (from Pfam)

Date:

2023-12-12

The structure of beta-ketoacyl synthase is similar to that of the thiolase family (Pfam:PF00108) and also chalcone synthase. The active site of beta-ketoacyl synthase is located between the N and C-terminal domains. The N-terminal domain contains most of the structures involved in dimer formation and also the active site cysteine [1]. [1]. 9482715. Crystal structure of beta-ketoacyl-acyl carrier protein synthase. II from E.coli reveals the molecular architecture of condensing. enzymes.. Huang W, Jia J, Edwards P, Dehesh K, Schneider G, Lindqvist Y;. EMBO J 1998;17:1183-1191. (from Pfam)

Date:

2024-04-03

Date:

2023-12-12