{PDOC51935} {PS51935; NLPC_P60} {BEGIN} *************************** * NlpC/P60 domain profile * *************************** NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Characterized members of this superfamily have diverse enzymatic functions, such as peptidases, amidases, transglutaminases and acetyltransferases. This divergent superfamily consists of four main families: P60-like, AcmB/LytN-like, YaeF/YiiX-like, and LRAT-like. The P60-like family typified by P60 and its obvious relatives includes the most commonly occuring versions of the superfmily, which are seen in most bacterial lineages. All characterized members of this family are peptidases, and they either hydrolyze the D-gamma-glutamyl-meso-diaminopimelate linkage or N-acetylmuramate-L- alanine linkage. The proteins of the P60-like family show extensive lineage- specific diversification in terms of their domain architectures. In many proteins the catalytic peptidase NlpC/p60 domain is fused to domains such as SH3 (see ), LysM (see ), and choline-binding ~(CBD) (see ) domains. These domains probably aid them in interactions with peptides, carbohydrates and lipids that are associated with the bacterial cell wall. The NlpC/P60 domain is also fused to other catalytic domains such as the polysaccharide-hydrolyzing lysozyme domain, and the JAB domain that has metallopeptidase activity. These are likely to function as two-headed enzymes that simulteanously attack different linkages in the murein [1,2]. The NlpC/P60 domain consists of ~110-140 residues and is a primitive papain- like peptidase in the CA clan of cysteine peptidase with a Cys/His/His catalytic triad and a conserved catalytic core [E1]. The NlpC/P60 domain can be classified as an alpha+beta fold with segregated alpha and beta regions and represents a new family of papain-like cysteine peptidase (see ). The NlpC/P60 domain adopts a much simpler topology, consisting of a six- stranded, central beta sheet and five alpha helices, compared to the classical eight-stranded central beta sheet and seven alpha helices of papain. However, the core of the papain-like cysteine proteases is retained in the NlpC/P60 domain and consists of one alpha helix (H3) and a five-stranded, antiparallel beta sheet (beta8, beta13, beta9, beta10 and beta11) [3,4]. The profile we developed covers the entire NlpC/P60 domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2020 / First entry. [ 1] Anantharaman V., Aravind L. "Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes." Genome Biol 4:R11-R11(2003). PubMed=12620121; DOI=10.1186/gb-2003-4-2-r11 [ 2] Xu Q., Rawlings N.D., Chiu H.-J., Jaroszewski L., Klock H.E., Knuth M.W., Miller M.D., Elsliger M.-A., Deacon A.M., Godzik A., Lesley S.A., Wilson I.A. "Structural analysis of papain-like NlpC/P60 superfamily enzymes with a circularly permuted topology reveals potential lipid binding sites." PLoS One. 6:E22013-E22013(2011). PubMed=21799766; DOI=10.1371/journal.pone.0022013 [ 3] Xu Q., Sudek S., McMullan D., Miller M.D., Geierstanger B., Jones D.H., Krishna S.S., Spraggon G., Bursalay B., Abdubek P., Acosta C., Ambing E., Astakhova T., Axelrod H.L., Carlton D., Caruthers J., Chiu H.-J., Clayton T., Deller M.C., Duan L., Elias Y., Elsliger M.A., Feuerhelm J., Grzechnik S.K., Hale J., Han G.W., Haugen J., Jaroszewski L., Jin K.K., Klock H.E., Knuth M.W., Kozbial P., Kumar A., Marciano D., Morse A.T., Nigoghossian E., Okach L., Oommachen S., Paulsen J., Reyes R., Rife C.L., Trout C.V., van den Bedem H., Weekes D., White A., Wolf G., Zubieta C., Hodgson K.O., Wooley J., Deacon A.M., Godzik A., Lesley S.A., Wilson I.A. "Structural basis of murein peptide specificity of a gamma-D-glutamyl-l-diamino acid endopeptidase." Structure 17:303-313(2009). PubMed=19217401; DOI=10.1016/j.str.2008.12.008 [ 4] Xu Q., Abdubek P., Astakhova T., Axelrod H.L., Bakolitsa C., Cai X., Carlton D., Chen C., Chiu H.-J., Chiu M., Clayton T., Das D., Deller M.C., Duan L., Ellrott K., Farr C.L., Feuerhelm J., Grant J.C., Grzechnik A., Han G.W., Jaroszewski L., Jin K.K., Klock H.E., Knuth M.W., Kozbial P., Krishna S.S., Kumar A., Lam W.W., Marciano D., Miller M.D., Morse A.T., Nigoghossian E., Nopakun A., Okach L., Puckett C., Reyes R., Tien H.J., Trame C.B., van den Bedem H., Weekes D., Wooten T., Yeh A., Hodgson K.O., Wooley J., Elsliger M.-A., Deacon A.M., Godzik A., Lesley S.A., Wilson I.A. "Structure of the gamma-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-gamma-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases." Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 66:1354-1364(2010). PubMed=20944232; DOI=10.1107/S1744309110021214 [E1] https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=C40 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}