PROSITE documentation PDOC51935NlpC/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-γ-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 <PDOC51781>), LysM (see <PDOC51782>), and choline-binding ~(CBD) (see <PDOC51170>) 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 α+β fold with segregated α and β regions and represents a new family of papain-like cysteine peptidase (see <PDB:2EVR>). The NlpC/P60 domain adopts a much simpler topology, consisting of a six-stranded, central β sheet and five α helices, compared to the classical eight-stranded central β sheet and seven α helices of papain. However, the core of the papain-like cysteine proteases is retained in the NlpC/P60 domain and consists of one α helix (H3) and a five-stranded, antiparallel β sheet (β8, β13, β9, β10 and β11) [3,4].
The profile we developed covers the entire NlpC/P60 domain.
Last update:August 2020 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Anantharaman V. Aravind L. |
| Title | Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes. | |
| Source | Genome Biol 4:R11-R11(2003). | |
| PubMed ID | 12620121 | |
| DOI | 10.1186/gb-2003-4-2-r11 |
| 2 | Authors | 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. |
| Title | Structural analysis of papain-like NlpC/P60 superfamily enzymes with a circularly permuted topology reveals potential lipid binding sites. | |
| Source | PLoS One. 6:E22013-E22013(2011). | |
| PubMed ID | 21799766 | |
| DOI | 10.1371/journal.pone.0022013 |
| 3 | Authors | 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. |
| Title | Structural basis of murein peptide specificity of a gamma-D-glutamyl-l-diamino acid endopeptidase. | |
| Source | Structure 17:303-313(2009). | |
| PubMed ID | 19217401 | |
| DOI | 10.1016/j.str.2008.12.008 |
| 4 | Authors | 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. |
| Title | 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. | |
| Source | Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 66:1354-1364(2010). | |
| PubMed ID | 20944232 | |
| DOI | 10.1107/S1744309110021214 |
| E1 | Title | https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=C40 |
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