1u8f: Difference between revisions

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[[Image:1u8f.gif|left|200px]]
{{Seed}}
[[Image:1u8f.png|left|200px]]


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{{STRUCTURE_1u8f|  PDB=1u8f  |  SCENE=  }}  
{{STRUCTURE_1u8f|  PDB=1u8f  |  SCENE=  }}  


'''Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution'''
===Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution===




==Overview==
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GAPDH (D-glyceraldehyde-3-phosphate dehydrogenase) is a multifunctional protein that is a target for the design of antitrypanosomatid and anti-apoptosis drugs. Here, the first high-resolution (1.75 Angstroms) structure of a human GAPDH is reported. The structure shows that the intersubunit selectivity cleft that has been leveraged in the design of antitrypanosomatid compounds is closed in human GAPDH. Modeling of an anti-trypanosomatid GAPDH inhibitor in the human GAPDH active site provides insights into the basis for the observed selectivity of this class of inhibitor. Moreover, the high-resolution data reveal a new feature of the cleft: water-mediated intersubunit hydrogen bonds that assist closure of the cleft in the human enzyme. The structure is used in a computational ligand-docking study of the small-molecule compound CGP-3466, which inhibits apoptosis by preventing nuclear accumulation of GAPDH. Plausible binding sites are identified in the adenosine pocket of the NAD(+)-binding site and in a hydrophobic channel located in the center of the tetramer near the intersection of the three molecular twofold axes. The structure is also used to build a qualitative model of the complex between GAPDH and the E3 ubiquitin ligase Siah1. The model suggests that the convex surface near GAPDH Lys227 interacts with a large shallow groove of the Siah1 dimer. These results are discussed in the context of the recently discovered NO-S-nitrosylation-GAPDH-Siah1 apoptosis cascade.
The line below this paragraph, {{ABSTRACT_PUBMED_16510976}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_16510976}}


==About this Structure==
==About this Structure==
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[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 10:53:36 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:51:49 2008''

Revision as of 07:51, 28 July 2008

File:1u8f.png

Template:STRUCTURE 1u8f

Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution

Template:ABSTRACT PUBMED 16510976

About this Structure

1U8F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase., Jenkins JL, Tanner JJ, Acta Crystallogr D Biol Crystallogr. 2006 Mar;62(Pt 3):290-301. Epub 2006, Feb 22. PMID:16510976

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