2i66
From Proteopedia
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| - | [[Image:2i66.gif|left|200px]] | + | [[Image:2i66.gif|left|200px]] |
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| - | '''Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis''' | + | {{Structure |
| + | |PDB= 2i66 |SIZE=350|CAPTION= <scene name='initialview01'>2i66</scene>, resolution 1.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=G1R:[(2R,3R,4R,5R)-5-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>G1R</scene> and <scene name='pdbligand=G2R:[(2R,3R,4R,5R)-5-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL [(2R,3S,4S)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHYL DIHYDROGEN DIPHOSPHATE'>G2R</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/NAD(+)_nucleosidase NAD(+) nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.5 3.2.2.5] | ||
| + | |GENE= CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2I66 is a [ | + | 2I66 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=2I66 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis., Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q, J Biol Chem. 2006 Oct 27;281(43):32861-9. Epub 2006 Sep 2. PMID:[http:// | + | Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis., Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q, J Biol Chem. 2006 Oct 27;281(43):32861-9. Epub 2006 Sep 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16951430 16951430] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: NAD(+) nucleosidase]] | [[Category: NAD(+) nucleosidase]] | ||
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[[Category: the catalytic pocket]] | [[Category: the catalytic pocket]] | ||
| - | ''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 17:25:54 2008'' |
Revision as of 15:25, 20 March 2008
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| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | CD38 (Homo sapiens) | ||||||
| Activity: | NAD(+) nucleosidase, with EC number 3.2.2.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis
Overview
The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules. By using NAD(+) and a surrogate substrate, NGD(+), we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu(226) rather than by a covalent linkage. The polar interactions between Glu(226) and the substrate 2',3'-OH groups are essential for initiating catalysis. Ser(193) was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design.
About this Structure
2I66 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis., Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q, J Biol Chem. 2006 Oct 27;281(43):32861-9. Epub 2006 Sep 2. PMID:16951430
Page seeded by OCA on Thu Mar 20 17:25:54 2008
