title: Structure based design of novel inhibitors for histidinol dehydrogenase from Geotrichum candidum.
abstract: Histidinol dehydrogenase, the product of the HisD gene, mediates the final step in the histidine biosynthetic pathway. This enzyme has captured attention for drug discovery studies in past few years. Recently, our group cloned and expressed Geotrichum candidum histidinol dehydrogenase and successful screening of substrate analog inhibitors of histidinol dehydrogenase led to some antifungal compounds with IC(50) values in micromolar range. In this study, we have done docking analysis of these antifungal agents in G. candidum. Two new compounds were designed based on the docking results and these compounds turned out to be potent inhibitors of G. candidum histidinol dehydrogenase, showing IC(50) values as low as 3.17 microM.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Punjab, India.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pahwa
authors.forename: Simranjeet
authors.initials: S
authors.lastname: Kaur
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Roy
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005848:Geotrichum / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase