1u8f
From Proteopedia
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| - | [[Image:1u8f.gif|left|200px]] | + | [[Image:1u8f.gif|left|200px]] |
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| - | '''Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution''' | + | {{Structure |
| + | |PDB= 1u8f |SIZE=350|CAPTION= <scene name='initialview01'>1u8f</scene>, resolution 1.75Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] | ||
| + | |GENE= GAPD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1U8F is a [ | + | 1U8F 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=1U8F OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16510976 16510976] |
[[Category: Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)]] | [[Category: Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:28:36 2008'' |
Revision as of 12:28, 20 March 2008
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| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | GAPD (Homo sapiens) | ||||||
| Activity: | Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating), with EC number 1.2.1.12 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution
Overview
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.
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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