3RO9: Candida glabrata dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3R)-3-[3-methoxy-5-(pyridin-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)

Citation:
Abstract
A novel strategy for targeting the pathogenic organisms Candida albicans and Candida glabrata focuses on the development of potent and selective antifolates effective against dihydrofolate reductase. Crystal structure analysis suggested that an essential loop at the active site (Thr 58-Phe 66) differs from the analogous residues in the human enzyme, potentially providing a mechanism for achieving selectivity. In order to probe the role of this loop, we employed chemical synthesis, crystal structure determination and molecular dynamics simulations. The results of these analyses show that the loop residues undergo ligand-induced conformational changes that are similar among the fungal and human species.
PDB ID: 3RO9Download
MMDB ID: 99329
PDB Deposition Date: 2011/4/25
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.596  Å
Source Organism:
Similar Structures:
Biological Unit for 3RO9: monomeric; determined by author and by software (PISA)
Molecular Components in 3RO9
Label Count Molecule
Protein (1 molecule)
1
Strain Cbs138 Chromosome J Complete Sequence
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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