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| [[Image:2i66.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2i66| PDB=2i66 | SCENE= }} | | {{STRUCTURE_2i66| PDB=2i66 | SCENE= }} |
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| '''Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis'''
| | ===Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_16951430}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16951430 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16951430}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[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 Sun May 4 07:07:22 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:20:57 2008'' |
