2i66
From Proteopedia
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[[Image:2i66.gif|left|200px]] | [[Image:2i66.gif|left|200px]] | ||
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| - | | | + | {{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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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] | 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: Single protein]] | [[Category: Single protein]] | ||
[[Category: Graeff, R.]] | [[Category: Graeff, R.]] | ||
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[[Category: Liu, Q.]] | [[Category: Liu, Q.]] | ||
[[Category: Munshi, C.]] | [[Category: Munshi, C.]] | ||
| - | [[Category: | + | [[Category: Reaction intermediate]] |
| - | [[Category: | + | [[Category: Reaction product]] |
| - | [[Category: | + | [[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 | + | |
Revision as of 04:07, 4 May 2008
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 Sun May 4 07:07:22 2008
