Burshteyn F

References (2)

Title : Structural genomics for drug design against the pathogen Coxiella burnetii - Franklin_2015_Proteins_83_2124
Author(s) : Franklin MC , Cheung J , Rudolph MJ , Burshteyn F , Cassidy M , Gary E , Hillerich B , Yao ZK , Carlier PR , Totrov M , Love JD
Ref : Proteins , 83 :2124 , 2015
Abstract : Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high-throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure-based drug design. This enzyme's structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDHFR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25-fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria. Proteins 2015; 83:2124-2136. (c) 2015 Wiley Periodicals, Inc.
ESTHER : Franklin_2015_Proteins_83_2124
PubMedSearch : Franklin_2015_Proteins_83_2124
PubMedID: 26033498
Gene_locus related to this paper: coxbu-CBU1769

Title : Structures of human acetylcholinesterase in complex with pharmacologically important ligands - Cheung_2012_J.Med.Chem_55_10282
Author(s) : Cheung J , Rudolph MJ , Burshteyn F , Cassidy MS , Gary EN , Love J , Franklin MC , Height JJ
Ref : Journal of Medicinal Chemistry , 55 :10282 , 2012
Abstract : Human acetylcholinesterase (AChE) is a significant target for therapeutic drugs. Here we present high resolution crystal structures of human AChE, alone and in complexes with drug ligands; donepezil, an Alzheimer's disease drug, binds differently to human AChE than it does to Torpedo AChE. These crystals of human AChE provide a more accurate platform for further drug development than previously available.
ESTHER : Cheung_2012_J.Med.Chem_55_10282
PubMedSearch : Cheung_2012_J.Med.Chem_55_10282
PubMedID: 23035744
Gene_locus related to this paper: human-ACHE