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Catalytic triad heterogeneity in S51 peptidase family: Structural basis for functional variability
Author(s) -
Yadav Pooja,
Goyal Venuka Durani,
Chandravanshi Khileshwari,
Kumar Ashwani,
Gokhale Sadashiv M.,
Jamdar Sahayog N.,
Makde Ravindra D.
Publication year - 2019
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25693
Subject(s) - triad (sociology) , catalytic triad , biology , catalysis , psychology , biochemistry , psychoanalysis , active site
Peptidase E (PepE) is a nonclassical serine peptidase with a Ser‐His‐Glu catalytic triad. It is specific for dipeptides with an N‐terminal aspartate residue (Asp‐X dipeptidase activity). Its homolog from Listeria monocytogenes (PepElm) has a Ser‐His‐Asn “catalytic triad.” Based on sequence alignment we predicted that the PepE homolog from Deinococcus radiodurans (PepEdr) would have a Ser‐His‐Asp “catalytic triad.” We confirmed this by solving the crystal structure of PepEdr to 2.7 Å resolution. We show that PepElm and PepEdr lack the Asp‐X dipeptidase activity. Our analyses suggest that absence of P1 pocket in the active site could be the main reason for this lack of typical activity. Sequence and structural data reveal that the PepE homologs can be divided into long and short PepEs based on presence or absence of a C‐terminal tail which adopts a β‐hairpin conformation in the canonical PepE from Salmonella enterica . A long PepE from Bacillus subtilis with Ser‐His‐Asp catalytic triad exhibits Asp‐X dipeptidase activity. Whereas the three long PepEs enzymatically characterized till date have been found to possess the Asp‐X dipeptidase activity, the three enzymatically characterized short PepEs lack this activity irrespective of the nature of their catalytic triads. This study illuminates the structural and functional heterogeneity in the S51 family and also provides structural basis for the functional variability among PepE homologs.