1b3o: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1b3o]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1B3O FirstGlance]. <br> | <table><tr><td colspan='2'>[[1b3o]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1B3O FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPR:6-CHLOROPURINE+RIBOSIDE,+5-MONOPHOSPHATE'>CPR</scene>, <scene name='pdbligand=SAE:SELENAZOLE-4-CARBOXYAMIDE-ADENINE+DINUCLEOTIDE'>SAE</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPR:6-CHLOROPURINE+RIBOSIDE,+5-MONOPHOSPHATE'>CPR</scene>, <scene name='pdbligand=SAE:SELENAZOLE-4-CARBOXYAMIDE-ADENINE+DINUCLEOTIDE'>SAE</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b3o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1b3o RCSB], [http://www.ebi.ac.uk/pdbsum/1b3o PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b3o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1b3o RCSB], [http://www.ebi.ac.uk/pdbsum/1b3o PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 31: | Line 31: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: IMP dehydrogenase]] | [[Category: IMP dehydrogenase]] | ||
[[Category: Colby, T D | [[Category: Colby, T D]] | ||
[[Category: Goldstein, B M | [[Category: Goldstein, B M]] | ||
[[Category: Strickler, M D | [[Category: Strickler, M D]] | ||
[[Category: Vanderveen, K | [[Category: Vanderveen, K]] | ||
[[Category: Dehydrogenase]] | [[Category: Dehydrogenase]] | ||
[[Category: Guanine nucleotide synthesis]] | [[Category: Guanine nucleotide synthesis]] | ||
[[Category: Impd]] | [[Category: Impd]] | ||
[[Category: Impdh]] | [[Category: Impdh]] | ||
Revision as of 14:35, 22 December 2014
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
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInosine 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
| ||||||||||||||||||