1ia1
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1ia1.gif|left|200px]] | + | [[Image:1ia1.gif|left|200px]] |
| - | + | ||
| - | '''Candida albicans dihydrofolate reductase complexed with dihydro-nicotinamide-adenine-dinucleotide phosphate (NADPH) and 5-(PHENYLSULFANYL)-2,4-QUINAZOLINEDIAMINE (GW997)''' | + | {{Structure |
| + | |PDB= 1ia1 |SIZE=350|CAPTION= <scene name='initialview01'>1ia1</scene>, resolution 1.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=TQ3:5-PHENYLSULFANYL-2,4-QUINAZOLINEDIAMINE'>TQ3</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] | ||
| + | |GENE= DFR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5476 Candida albicans]) | ||
| + | }} | ||
| + | |||
| + | '''Candida albicans dihydrofolate reductase complexed with dihydro-nicotinamide-adenine-dinucleotide phosphate (NADPH) and 5-(PHENYLSULFANYL)-2,4-QUINAZOLINEDIAMINE (GW997)''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1IA1 is a [ | + | 1IA1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IA1 OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11520201 11520201] |
[[Category: Candida albicans]] | [[Category: Candida albicans]] | ||
[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
| Line 24: | Line 33: | ||
[[Category: reductase]] | [[Category: reductase]] | ||
| - | ''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 11:47:33 2008'' |
Revision as of 09:47, 20 March 2008
| |||||||
| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | DFR1 (Candida albicans) | ||||||
| Activity: | Dihydrofolate reductase, with EC number 1.5.1.3 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Candida albicans dihydrofolate reductase complexed with dihydro-nicotinamide-adenine-dinucleotide phosphate (NADPH) and 5-(PHENYLSULFANYL)-2,4-QUINAZOLINEDIAMINE (GW997)
Overview
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.
About this Structure
1IA1 is a Single protein structure of sequence from Candida albicans. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 11:47:33 2008
