1pjp
From Proteopedia
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'''THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE''' | '''THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE''' | ||
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[[Category: Strobl, S.]] | [[Category: Strobl, S.]] | ||
[[Category: Wang, Z M.]] | [[Category: Wang, Z M.]] | ||
| - | [[Category: | + | [[Category: Angiotensin]] |
| - | [[Category: | + | [[Category: Dipeptidyl carboxypeptidase]] |
| - | [[Category: | + | [[Category: Human chymase]] |
| - | [[Category: | + | [[Category: Serine proteinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:09:47 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:09, 3 May 2008
THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE
Overview
Human chymase (HC) is a chymotrypsin-like serine proteinase expressed by mast cells. The 2.2 A crystal structure of HC complexed to the peptidyl inhibitor, succinyl-Ala-Ala-Pro-Phe-chloromethylketone (CMK), was solved and refined to a crystallographic R-factor of 18.4 %. The HC structure exhibits the typical folding pattern of a chymotrypsin-like serine proteinase, and shows particularly similarity to rat chymase 2 (rat mast cell proteinase II) and human cathepsin G. The peptidyl-CMK inhibitor is covalently bound to the active-site residues Ser195 and His57; the peptidyl moiety juxtaposes the S1 entrance frame segment 214-217 by forming a short antiparallel beta-sheet. HC is a highly efficient angiotensin-converting enzyme. Modeling of the chymase-angiotensin I interaction guided by the geometry of the bound chloromethylketone inhibitor indicates that the extended substrate binding site contains features that may generate the dipeptidyl carboxypeptidase-like activity needed for efficient cleavage and activation of the hormone. The C-terminal carboxylate group of angiotensin I docked into the active-site cleft, with the last two residues extending beyond the active site, is perfectly localized to make a favorable hydrogen bond and salt bridge with the amide nitrogen of the Lys40-Phe41 peptide bond and with the epsilon-ammonium group of the Lys40 side-chain. This amide positioning is unique to the chymase-related proteinases, and only chymases from primates possess a Lys residue at position 40. Thus, the structure conveniently explains the preferred conversion of angiotensin I to angiotensin II by human chymase.
About this Structure
1PJP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity., Pereira PJ, Wang ZM, Rubin H, Huber R, Bode W, Schechter NM, Strobl S, J Mol Biol. 1999 Feb 12;286(1):163-73. PMID:9931257 Page seeded by OCA on Sat May 3 05:09:47 2008
