This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1b3o
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1b3o |SIZE=350|CAPTION= <scene name='initialview01'>1b3o</scene>, resolution 2.90Å | |PDB= 1b3o |SIZE=350|CAPTION= <scene name='initialview01'>1b3o</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CPR:6-CHLOROPURINE+RIBOSIDE,+5'-MONOPHOSPHATE'>CPR</scene>, <scene name='pdbligand=SAE:SELENAZOLE-4-CARBOXYAMIDE-ADENINE+DINUCLEOTIDE'>SAE</scene> | + | |LIGAND= <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> |
| - | |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] | + | |ACTIVITY= <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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<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.ebi.ac.uk/pdbsum/1b3o PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1b3o RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Strickler, M D.]] | [[Category: Strickler, M D.]] | ||
[[Category: Vanderveen, K.]] | [[Category: Vanderveen, K.]] | ||
| - | [[Category: CPR]] | ||
| - | [[Category: SAE]] | ||
| - | [[Category: UNX]] | ||
[[Category: dehydrogenase]] | [[Category: dehydrogenase]] | ||
[[Category: guanine nucleotide synthesis]] | [[Category: guanine nucleotide synthesis]] | ||
| Line 35: | Line 35: | ||
[[Category: impdh]] | [[Category: impdh]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:52:52 2008'' |
Revision as of 15:52, 30 March 2008
| |||||||
| , resolution 2.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | IMP dehydrogenase, with EC number 1.1.1.205 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
Page seeded by OCA on Sun Mar 30 18:52:52 2008
