1orf

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[[Image:1orf.jpg|left|200px]]
[[Image:1orf.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1orf |SIZE=350|CAPTION= <scene name='initialview01'>1orf</scene>, resolution 2.40&Aring;
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The line below this paragraph, containing "STRUCTURE_1orf", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=MAI:DEOXO-METHYLARGININE'>MAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Granzyme_A Granzyme A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.78 3.4.21.78] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= GZMA OR CTLA3 OR HFSP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_1orf| PDB=1orf | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1orf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1orf OCA], [http://www.ebi.ac.uk/pdbsum/1orf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1orf RCSB]</span>
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}}
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'''The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity'''
'''The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity'''
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[[Category: Harris, J L.]]
[[Category: Harris, J L.]]
[[Category: Mahrus, S.]]
[[Category: Mahrus, S.]]
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[[Category: hydrolase]]
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[[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 Sun Mar 30 22:49:15 2008''
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Revision as of 01:11, 3 May 2008

Template:STRUCTURE 1orf

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


Overview

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.

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 Page seeded by OCA on Sat May 3 04:11:29 2008

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