1pjp
From Proteopedia
(New page: 200px<br /> <applet load="1pjp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pjp, resolution 2.2Å" /> '''THE 2.2 A CRYSTAL ST...) |
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caption="1pjp, resolution 2.2Å" /> | caption="1pjp, resolution 2.2Å" /> | ||
'''THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE'''<br /> | '''THE 2.2 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH SUCCINYL-ALA-ALA-PRO-PHE-CHLOROMETHYLKETONE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human chymase (HC) is a chymotrypsin-like serine proteinase expressed by | + | 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== | ==About this Structure== | ||
| - | 1PJP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chymase Chymase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.39 3.4.21.39] Full crystallographic information is available from [http:// | + | 1PJP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chymase Chymase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.39 3.4.21.39] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
| - | [[Category: Pereira, P | + | [[Category: Pereira, P J.B.]] |
[[Category: Rubin, H.]] | [[Category: Rubin, H.]] | ||
| - | [[Category: Schechter, N | + | [[Category: Schechter, N M.]] |
[[Category: Strobl, S.]] | [[Category: Strobl, S.]] | ||
| - | [[Category: Wang, Z | + | [[Category: Wang, Z M.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:29:33 2008'' |
Revision as of 12:29, 21 February 2008
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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 with and as ligands. Active as Chymase, with EC number 3.4.21.39 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
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