1orf

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[[Image:1orf.jpg|left|200px]]<br /><applet load="1orf" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1orf.jpg|left|200px]]
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caption="1orf, resolution 2.40&Aring;" />
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'''The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity'''<br />
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{{Structure
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|PDB= 1orf |SIZE=350|CAPTION= <scene name='initialview01'>1orf</scene>, resolution 2.40&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
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|ACTIVITY= [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]
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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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'''The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1ORF 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORF OCA].
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1ORF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORF OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12819769 12819769]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12819769 12819769]
[[Category: Granzyme A]]
[[Category: Granzyme A]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: hydrolase]]
[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:20:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:14:33 2008''

Revision as of 11:14, 20 March 2008

Image:1orf.jpg


PDB ID 1orf

Drag the structure with the mouse to rotate
, resolution 2.40Å
Ligands:
Gene: GZMA OR CTLA3 OR HFSP (Homo sapiens)
Activity: Granzyme A, with EC number 3.4.21.78
Coordinates: save as pdb, mmCIF, xml



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

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