1b3o
From Proteopedia
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| - | [[Image:1b3o.gif|left|200px]] | + | [[Image:1b3o.gif|left|200px]] |
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| - | '''TERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDE''' | + | {{Structure |
| + | |PDB= 1b3o |SIZE=350|CAPTION= <scene name='initialview01'>1b3o</scene>, resolution 2.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CPR:6-CHLOROPURINE+RIBOSIDE,+5'-MONOPHOSPHATE'>CPR</scene>, <scene name='pdbligand=SAE:SELENAZOLE-4-CARBOXYAMIDE-ADENINE+DINUCLEOTIDE'>SAE</scene> and <scene name='pdbligand=UNX:UNKNOWN ATOM OR ION'>UNX</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''TERNARY COMPLEX OF HUMAN TYPE-II INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP AND SELENAZOLE ADENINE DINUCLEOTIDE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1B3O is a [ | + | 1B3O 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=1B3O OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10097070 10097070] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: IMP dehydrogenase]] | [[Category: IMP dehydrogenase]] | ||
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[[Category: impdh]] | [[Category: impdh]] | ||
| - | ''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 10:05:47 2008'' |
Revision as of 08:05, 20 March 2008
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| , resolution 2.90Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | IMP dehydrogenase, with EC number 1.1.1.205 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
About this Structure
1B3O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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