Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Abstract Text:

Qun Liu,Irina A Kriksunov,Richard Graeff,Cyrus Munshi,Hon Cheung Lee,Quan Hao,

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.

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Publishing Authors By Initials

Q Liu,IA Kriksunov,R Graeff,C Munshi,HC Lee,Q Hao,

For similar water research abstracts see: water research

PUBMED ID PMID:

MEDLINE DATE:

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 32861-9

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 2

MONTH: 09

YEAR: 2006

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Keywords Mesh Terms:

KEYWORDS: Water

MESH TERMS: chemistry

Chemical & Substance for Abstract: Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis. Information

Substance Name: NAD+ Nucleosidase

Registry Number: EC 3.2.2.5

Grant and Affiliation Information for Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.

AFFILIATION: Macromolecular Diffraction Facility at the Cornell High Energy Synchrotron Source (MacCHESS), Cornell University, Ithaca, NY 14853, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR 01646

ACRONYM: RR

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis Related Publications

• A study of Dr. Gao Huiyuan's new prescriptions.
• Normative standards for vocal tract dimensions by race as measured by acoustic pharyngometry.
• Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.
• [A morphological study of chondrogenesis by adipose-derived adult stem cells induced by recombinant human bone morphogenetic protein 2]
• [Age-related changes of the function and amount of natural killer cells in the liver: experiment with mice]
• [Building artificial neural networks model on portable NIR integrity wheat component measuring apparatus]
• [Chemical constituents from Viscum nudum and their accelerating PC12 cell differentiation]
• [Clinical analysis of the infection with human papillomavirus in women]
• [Clinical and laboratory study of a case of hematidrosis]
• [Coronary artery bypass graft for patients with ascending aorta atherosclerosis]
• [Detection of the gene-deleted female carriers of Duchenne/Becker muscular dystrophy using a fluorescent in situ hybridization based method]
• [Dislocation of intraocular lens inferior loop and ciliochoroidal detachment caused by blunt contusion: a report of two cases]
• [Evaluation study on determination of ZPP in blood with hematofluorometer]
• [Helical structure revealed upon the beta heterochromatin of polytene chromosome of Drosophila virilis]
• [Improving the alertness of large granular lymphocytic leukemia]
• [Influence of transfected EGFR-cDNA on bcl-2 and Bax in glioblastoma cells]
• [Intergeneric somatic hybridization between Astragalus adsurgens Pall and Medicago sativa L.]
• [Long-term results of prosthetic mitral valve replacement with home-made tilting disc valve: a report of 125 cases]
• [Morphological and anatomical characterization of a stripe mutant with abnormal floral organs in rice]
• [Preparation and properties of complex of europium lanthanum with crown ether and p-phthalic acid]
• [Prospective randomized trial of prophylaxis of postoperative peritoneal carcinomatosis of advanced gastric cancer: intraperitoneal chemotherapy with mitomycin C bound to activated carbon particles]
• [Study of gene expression profiling in breast cancer by DNA microarray]
• [Study on large-scale CD34+ cell enrichment using immunomagnetic isolation apparatus]
• [Study on the distribution of vitamin D receptor gene start codon polymorphism in the Achangs and Hans]
• [Study on the seroepidemiology of Rickettsia infection in Henan province, 2004]
• [The expression of EST and ER in hemangioma with its clinical value]
• [The influence of KCl on SERS of fuchsin basic in silver colloids]
• [Two new flavones from Fordia cauliflora of Yunnan]
• [Ultrastructural localization of transcription sites of rRNA genes in the nucleolus of wheat]
• [Virological and clinical features of patients with sporadic hepatitis C]