2i66
From Proteopedia
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|PDB= 2i66 |SIZE=350|CAPTION= <scene name='initialview01'>2i66</scene>, resolution 1.70Å | |PDB= 2i66 |SIZE=350|CAPTION= <scene name='initialview01'>2i66</scene>, resolution 1.70Å | ||
|SITE= | |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> | + | |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>, <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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2i65|2I65]], [[2i67|2I67]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i66 OCA], [http://www.ebi.ac.uk/pdbsum/2i66 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2i66 RCSB]</span> | ||
}} | }} | ||
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[[Category: Liu, Q.]] | [[Category: Liu, Q.]] | ||
[[Category: Munshi, C.]] | [[Category: Munshi, C.]] | ||
| - | [[Category: G1R]] | ||
| - | [[Category: G2R]] | ||
[[Category: reaction intermediate]] | [[Category: reaction intermediate]] | ||
[[Category: reaction product]] | [[Category: reaction product]] | ||
[[Category: the catalytic pocket]] | [[Category: the catalytic pocket]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:40:15 2008'' |
Revision as of 00:40, 31 March 2008
| |||||||
| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CD38 (Homo sapiens) | ||||||
| Activity: | NAD(+) nucleosidase, with EC number 3.2.2.5 | ||||||
| Related: | 2I65, 2I67
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
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