1b3o: Difference between revisions

Revision as of 18:10, 30 June 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1b3o.png

Template:STRUCTURE 1b3o

TERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDETERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDE

Template:ABSTRACT PUBMED 10097070

About this StructureAbout this Structure

1B3O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design., Colby TD, Vanderveen K, Strickler MD, Markham GD, Goldstein BM, Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3531-6. PMID:10097070

Page seeded by OCA on Mon Jun 30 18:10:12 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1b3o.gif|left|200px]]
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 {{STRUCTURE_1b3o|  PDB=1b3o  |  SCENE=  }}
-'''TERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDE'''
+===TERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDE===
-==Overview==
+<!--
-Inosine monophosphate dehydrogenase (IMPDH) controls a key metabolic step in the regulation of cell growth and differentiation. This step is the NAD-dependent oxidation of inosine 5' monophosphate (IMP) to xanthosine 5' monophosphate, the rate-limiting step in the synthesis of the guanine nucleotides. Two isoforms of IMPDH have been identified, one of which (type II) is significantly up- regulated in neoplastic and differentiating cells. As such, it has been identified as a major target in antitumor and immunosuppressive drug design. We present here the 2.9-A structure of a ternary complex of the human type II isoform of IMPDH. The complex contains the substrate analogue 6-chloropurine riboside 5'-monophosphate (6-Cl-IMP) and the NAD analogue selenazole-4-carboxamide adenine dinucleotide, the selenium derivative of the active metabolite of the antitumor drug tiazofurin. The enzyme forms a homotetramer, with the dinucleotide binding at the monomer-monomer interface. The 6 chloro-substituted purine base is dehalogenated, forming a covalent adduct at C6 with Cys-331. The dinucleotide selenazole base is stacked against the 6-Cl-IMP purine ring in an orientation consistent with the B-side stereochemistry of hydride transfer seen with NAD. The adenosine end of the ligand interacts with residues not conserved between the type I and type II isoforms, suggesting strategies for the design of isoform-specific agents.
+The line below this paragraph, {{ABSTRACT_PUBMED_10097070}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 10097070 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_10097070}}
 ==About this Structure==
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 [[Category: Impd]]
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