1lrt
From Proteopedia
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|PDB= 1lrt |SIZE=350|CAPTION= <scene name='initialview01'>1lrt</scene>, resolution 2.20Å | |PDB= 1lrt |SIZE=350|CAPTION= <scene name='initialview01'>1lrt</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TAD:BETA-METHYLENE-THIAZOLE-4-CARBOXYAMIDE-ADENINE+DINUCLEOTIDE'>TAD</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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= IMPDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5724 Tritrichomonas foetus]) | |GENE= IMPDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5724 Tritrichomonas foetus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1ak5|1AK5]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lrt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lrt OCA], [http://www.ebi.ac.uk/pdbsum/1lrt PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lrt RCSB]</span> | ||
}} | }} | ||
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[[Category: Hedstrom, L.]] | [[Category: Hedstrom, L.]] | ||
[[Category: Petsko, G A.]] | [[Category: Petsko, G A.]] | ||
| - | [[Category: BOG]] | ||
| - | [[Category: IMP]] | ||
| - | [[Category: K]] | ||
| - | [[Category: TAD]] | ||
| - | [[Category: TRS]] | ||
[[Category: alpha-beta barrel]] | [[Category: alpha-beta barrel]] | ||
[[Category: flap]] | [[Category: flap]] | ||
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[[Category: ternary complex]] | [[Category: ternary complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:06:35 2008'' |
Revision as of 19:06, 30 March 2008
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| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | IMPDH (Tritrichomonas foetus) | ||||||
| Activity: | IMP dehydrogenase, with EC number 1.1.1.205 | ||||||
| Related: | 1AK5
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF TERNARY COMPLEX OF TRITRICHOMONAS FOETUS INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE: STRUCTURAL CHARACTERIZATION OF NAD+ SITE IN MICROBIAL ENZYME
Overview
Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the conversion of IMP to XMP with the reduction of NAD(+), which is the rate-limiting step in the biosynthesis of guanine nucleotides. IMPDH is a promising target for chemotherapy. Microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid (MPA) and thiazole-4-carboxamide adenine dinucleotide (TAD). Part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD(+) binding site that is postulated to involve an active site flap. To understand the structural basis of the drug selectivity, we solved the X-ray crystal structure of the catalytic core domain of Tritrichomonas foetus IMPDH in complex with IMP and beta-methylene-TAD at 2.2 A resolution. Unlike previous structures of this enzyme, the active site loop is ordered in this complex, and the catalytic Cys319 is 3.6 A from IMP, in the same plane as the hypoxanthine ring. The active site loop forms hydrogen bonds to the carboxamide of beta-Me-TAD which suggests that NAD(+) promotes the nucleophillic attack of Cys319 on IMP. The interactions of the adenosine end of TAD are very different from those in the human enzyme, suggesting the NAD(+) site may be an exploitable target for the design of antimicrobial drugs. In addition, a new K(+) site is observed at the subunit interface. This site is adjacent to beta-Me-TAD, consistent with the link between the K(+) activation and NAD(+). However, contrary to the coupling model, the flap does not cover the adenosine subsite and remains largely disordered.
About this Structure
1LRT is a Single protein structure of sequence from Tritrichomonas foetus. Full crystallographic information is available from OCA.
Reference
Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis., Gan L, Petsko GA, Hedstrom L, Biochemistry. 2002 Nov 5;41(44):13309-17. PMID:12403633
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