1ia2

Candida albicans dihydrofolate reductase complexed with dihydro-nicotinamide-adenine-dinucleotide phosphate (NADPH) and 5-[(4-METHYLPHENYL)SULFANYL]-2,4-QUINAZOLINEDIAMINE (GW578)

spinqualitylabelsall models 1ia2, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ia2 is a 2 chain structure with sequence from Candida albicans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.82Å Ligands: MES, NDP, TQ4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DYR_CANAX Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. 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 PubMed X-ray crystallographic analysis of 5-(4'-substituted phenyl)sulfanyl-2,4-diaminoquinazoline inhibitors in ternary complex with Candida albicans dihydrofolate reductase (DHFR) and NADPH revealed two distinct modes of binding. The two compounds with small 4'-substituents (H and CH3) were found to bind with the phenyl group oriented in the plane of the quinazoline ring system and positioned adjacent to the C-helix. In contrast, the more selective inhibitors with larger 4'-substituents (tert-butyl and N-morpholino) were bound to the enzyme with the phenyl group perpendicular to the quinazoline ring and positioned in the region of the active site that typically binds the dihydronicotinamide moiety of NADPH. The cofactor appeared bound to DHFR but with the disordered dihydronicotinamide swung away from the protein surface and into solution. This unusual inhibitor binding mode may play an important role in the high DHFR selectivity of these compounds and also may provide new ideas for inhibitor design. X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.,Whitlow M, Howard AJ, Stewart D, Hardman KD, Chan JH, Baccanari DP, Tansik RL, Hong JS, Kuyper LF J Med Chem. 2001 Aug 30;44(18):2928-32. PMID:11520201 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydrofolate reductase 3D structures

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