2i67: Difference between revisions
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[[Image:2i67.gif|left|200px]] | [[Image:2i67.gif|left|200px]] | ||
'''Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis''' | {{Structure | ||
|PDB= 2i67 |SIZE=350|CAPTION= <scene name='initialview01'>2i67</scene>, resolution 1.71Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</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== | ||
2I67 is a [ | 2I67 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=2I67 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 17:25:56 2008'' | ||
Revision as of 15:25, 20 March 2008
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| 2i67, resolution 1.71Å | |||||||||||||
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| Ligands: | APR | ||||||||||||
| 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
2I67 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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