1orf

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[[Image:1orf.jpg|left|200px]]
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{{Seed}}
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{{STRUCTURE_1orf| PDB=1orf | SCENE= }}
{{STRUCTURE_1orf| PDB=1orf | SCENE= }}
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'''The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity'''
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===The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity===
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==Overview==
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The cell death-inducing serine protease granzyme A (GzmA) has a unique disulfide-linked quaternary structure. The structure of human GzmA bound to a tripeptide CMK inhibitor, determined at a resolution of 2.4 A, reveals that the oligomeric state contributes to substrate selection by limiting access to the active site for potential macromolecular substrates and inhibitors. Unlike other serine proteases, tetrapeptide substrate preferences do not correlate well with natural substrate cleavage sequences. This suggests that the context of the cleavage sequence within a macromolecular substrate imposes another level of selection not observed with the peptide substrates. Modeling of inhibitors bound to the GzmA active site shows that the dimer also contributes to substrate specificity in a unique manner by extending the active-site cleft. The crystal structure, along with substrate library profiling and mutagenesis, has allowed us to identify and rationally manipulate key components involved in GzmA substrate specificity.
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The line below this paragraph, {{ABSTRACT_PUBMED_12819769}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12819769 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12819769}}
==About this Structure==
==About this Structure==
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[[Category: Mahrus, S.]]
[[Category: Mahrus, S.]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:11:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:27:32 2008''

Revision as of 02:27, 29 July 2008

Image:1orf.png

Template:STRUCTURE 1orf

The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity

Template:ABSTRACT PUBMED 12819769

About this Structure

1ORF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity., Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS, Nat Struct Biol. 2003 Jul;10(7):527-34. PMID:12819769

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