2c02

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[[Image:2c02.gif|left|200px]]
[[Image:2c02.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2c02 |SIZE=350|CAPTION= <scene name='initialview01'>2c02</scene>, resolution 2.00&Aring;
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The line below this paragraph, containing "STRUCTURE_2c02", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Acy+Binding+Site+For+Chain+A'>AC1</scene>
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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=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</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/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_2c02| PDB=2c02 | 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=2c02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c02 OCA], [http://www.ebi.ac.uk/pdbsum/2c02 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c02 RCSB]</span>
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}}
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'''CRYSTAL STRUCTURES OF EOSINOPHIL-DERIVED NEUROTOXIN IN COMPLEX WITH THE INHIBITORS 5'-ATP, AP3A, AP4A AND AP5A'''
'''CRYSTAL STRUCTURES OF EOSINOPHIL-DERIVED NEUROTOXIN IN COMPLEX WITH THE INHIBITORS 5'-ATP, AP3A, AP4A AND AP5A'''
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[[Category: Swaminathan, G J.]]
[[Category: Swaminathan, G J.]]
[[Category: 5'-atp]]
[[Category: 5'-atp]]
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[[Category: ap3a]]
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[[Category: Ap3a]]
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[[Category: ap4a]]
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[[Category: Ap4a]]
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[[Category: ap5a]]
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[[Category: Ap5a]]
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[[Category: chemotaxis]]
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[[Category: Chemotaxis]]
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[[Category: endonuclease]]
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[[Category: Endonuclease]]
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[[Category: eosinophil]]
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[[Category: Eosinophil]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: hydrolase]]
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[[Category: Hydrolase]]
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[[Category: inhibitor]]
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[[Category: Inhibitor]]
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[[Category: nuclease]]
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[[Category: Nuclease]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: ribonuclease]]
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[[Category: Ribonuclease]]
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[[Category: rnase us]]
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[[Category: Rnase us]]
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[[Category: rnase-2]]
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[[Category: Rnase-2]]
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[[Category: sensory transduction]]
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[[Category: Sensory transduction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:02:19 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:14:17 2008''
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Revision as of 18:02, 3 May 2008

Template:STRUCTURE 2c02

CRYSTAL STRUCTURES OF EOSINOPHIL-DERIVED NEUROTOXIN IN COMPLEX WITH THE INHIBITORS 5'-ATP, AP3A, AP4A AND AP5A


Overview

Eosinophil-derived neurotoxin (EDN) is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. To probe the importance of this enzymatic activity further, specific inhibitors will be of great aid. Derivatives of 5'-ADP are among the most potent inhibitors currently known. Here, we use X-ray crystallography to investigate the binding of four natural nucleotides containing this moiety. 5'-ATP binds in two alternative orientations, one occupying the B2 subsite in a conventional manner and one being a retro orientation with no ordered adenosine moiety. Diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) bind with one adenine positioned at the B2 subsite, the polyphosphate chain extending across the P1 subsite in an ill-defined conformation, and a disordered second adenosine moiety. Diadenosine pentaphosphate (Ap5A), the most avid inhibitor of this series, binds in a completely ordered fashion with one adenine positioned conventionally at the B2 subsite, the polyphosphate chain occupying the P1 and putative P(-1) subsites, and the other adenine bound in a retro-like manner at the edge of the B1 subsite. The binding mode of each of these inhibitors has features seen in previously determined structures of adenosine diphosphates. We examine the structure-affinity relationships of these inhibitors and discuss the implications for the design of improved inhibitors.

About this Structure

2C02 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A., Baker MD, Holloway DE, Swaminathan GJ, Acharya KR, Biochemistry. 2006 Jan 17;45(2):416-26. PMID:16401072 Page seeded by OCA on Sat May 3 21:02:19 2008

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