3n2z
From Proteopedia
The Structure of Human Prolylcarboxypeptidase at 2.80 Angstroms Resolution
Structural highlights
Function[PCP_HUMAN] Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH. Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBACKGROUND: The unique S28 family of proteases is comprised of the carboxypeptidase PRCP and the aminopeptidase DPP7. The structural basis of the different substrate specificities of the two enzymes is not understood nor has the structure of the S28 fold been described. RESULTS: The experimentally phased 2.8 A crystal structure is presented for human PRCP. PRCP contains an alpha/beta hydrolase domain harboring the catalytic Asp-His-Ser triad and a novel helical structural domain that caps the active site. Structural comparisons with prolylendopeptidase and DPP4 identify the S1 proline binding site of PRCP. A structure-based alignment with the previously undescribed structure of DPP7 illuminates the mechanism of orthogonal substrate specificity of PRCP and DPP7. PRCP has an extended active-site cleft that can accommodate proline substrates with multiple N-terminal residues. In contrast, the substrate binding groove of DPP7 is occluded by a short amino-acid insertion unique to DPP7 that creates a truncated active site selective for dipeptidyl proteolysis of N-terminal substrates. CONCLUSION: The results define the structure of the S28 family of proteases, provide the structural basis of PRCP and DPP7 substrate specificity and enable the rational design of selective PRCP modulators. Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidase.,Soisson SM, Patel SB, Abeywickrema PD, Byrne NJ, Diehl RE, Hall DL, Ford RE, Reid JC, Rickert KW, Shipman JM, Sharma S, Lumb KJ BMC Struct Biol. 2010 Jun 11;10:16. PMID:20540760[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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