2rdl
From Proteopedia
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caption="2rdl, resolution 2.500Å" /> | caption="2rdl, resolution 2.500Å" /> | ||
'''Hamster Chymase 2'''<br /> | '''Hamster Chymase 2'''<br /> | ||
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| + | ==Overview== | ||
| + | Divergence of substrate specificity within the context of a common, structural framework represents an important mechanism by which new enzyme, activity naturally evolves. We present enzymological and X-ray structural, data for hamster chymase-2 (HAM2) that provides a detailed explanation for, the unusual hydrolytic specificity of this rodent alpha-chymase. In, enzymatic characterization, hamster chymase-1 (HAM1) showed typical, chymase proteolytic activity. In contrast, HAM2 exhibited atypical, substrate specificity, cleaving on the carboxyl side of the P1 substrate, residues Ala and Val, characteristic of elastolytic rather than, chymotryptic specificity. The 2.5 A resolution crystal structure of HAM2, complexed to the peptidyl inhibitor, MeOSuc-Ala-Ala-Pro-Ala-chloromethylketone revealed a narrow and shallow S1, substrate binding pocket that accommodated only a small hydrophobic, residue (e.g. Ala or Val). The different substrate specificities of HAM2, and HAM1 are explained by changes in four S1 substrate site residues, (positions 189, 190, 216 and 226). Of these, Asn189, Val190 and Val216, form an easily identifiable triplet in all known rodent alpha-chymases, that can be used to predict elastolytic specificity for novel chymase-like, sequences. Phylogenetic comparison defines guinea pig and rabbit chymases, as the closest orthologs to rodent alpha-chymases. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2RDL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RDL OCA]. | + | 2RDL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Msu+Binding+Site+For+Residue+I+1'>AC1</scene>, <scene name='pdbsite=AC2:Msu+Binding+Site+For+Residue+J+1'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Residue+A+246'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Residue+B+246'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Residue+A+247'>AC5</scene> and <scene name='pdbsite=AC6:So4+Binding+Site+For+Residue+B+247'>AC6</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RDL OCA]. |
| + | |||
| + | ==Reference== | ||
| + | Structural basis for elastolytic substrate specificity in rodent alpha -chymases., Kervinen J, Abad M, Crysler C, Kolpak M, Mahan AD, Masucci JA, Bayoumy S, Cummings MD, Yao X, Olson M, de Garavilla L, Kuo L, Deckman I, Spurlino J, J Biol Chem. 2007 Oct 31;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17981788 17981788] | ||
[[Category: Mesocricetus auratus]] | [[Category: Mesocricetus auratus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 17:29:11 2008'' |
Revision as of 15:29, 6 February 2008
|
Hamster Chymase 2
Overview
Divergence of substrate specificity within the context of a common, structural framework represents an important mechanism by which new enzyme, activity naturally evolves. We present enzymological and X-ray structural, data for hamster chymase-2 (HAM2) that provides a detailed explanation for, the unusual hydrolytic specificity of this rodent alpha-chymase. In, enzymatic characterization, hamster chymase-1 (HAM1) showed typical, chymase proteolytic activity. In contrast, HAM2 exhibited atypical, substrate specificity, cleaving on the carboxyl side of the P1 substrate, residues Ala and Val, characteristic of elastolytic rather than, chymotryptic specificity. The 2.5 A resolution crystal structure of HAM2, complexed to the peptidyl inhibitor, MeOSuc-Ala-Ala-Pro-Ala-chloromethylketone revealed a narrow and shallow S1, substrate binding pocket that accommodated only a small hydrophobic, residue (e.g. Ala or Val). The different substrate specificities of HAM2, and HAM1 are explained by changes in four S1 substrate site residues, (positions 189, 190, 216 and 226). Of these, Asn189, Val190 and Val216, form an easily identifiable triplet in all known rodent alpha-chymases, that can be used to predict elastolytic specificity for novel chymase-like, sequences. Phylogenetic comparison defines guinea pig and rabbit chymases, as the closest orthologs to rodent alpha-chymases.
About this Structure
2RDL is a Single protein structure of sequence from Mesocricetus auratus with as ligand. Known structural/functional Sites: , , , , and . Full crystallographic information is available from OCA.
Reference
Structural basis for elastolytic substrate specificity in rodent alpha -chymases., Kervinen J, Abad M, Crysler C, Kolpak M, Mahan AD, Masucci JA, Bayoumy S, Cummings MD, Yao X, Olson M, de Garavilla L, Kuo L, Deckman I, Spurlino J, J Biol Chem. 2007 Oct 31;. PMID:17981788
Page seeded by OCA on Wed Feb 6 17:29:11 2008
