5ou2

M. thermoresistible IMPDH in complex with IMP and Compound 2 (NMR744)M. thermoresistible IMPDH in complex with IMP and Compound 2 (NMR744)

Structural highlights 5ou2 is a 1 chain structure with sequence from Myct3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Gene: guaB, KEK_23061 (MYCT3) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [G7CNL4_MYCT3] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964] Publication Abstract from PubMed Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5'-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible ( Mth) IMPDH DeltaCBS inhibitors identified a low affinity phenylimidazole derivative. X-ray crystallography of the Mth IMPDH DeltaCBS-IMP-inhibitor complex revealed that two molecules of the fragment were bound in the NAD binding pocket of IMPDH. Linking the two molecules of the fragment afforded compounds with more than 1000-fold improvement in IMPDH affinity over the initial fragment hit. Fragment-Based Approach to Targeting Inosine-5'-monophosphate Dehydrogenase (IMPDH) from Mycobacterium tuberculosis.,Trapero A, Pacitto A, Singh V, Sabbah M, Coyne AG, Mizrahi V, Blundell TL, Ascher DB, Abell C J Med Chem. 2018 Mar 23. doi: 10.1021/acs.jmedchem.7b01622. PMID:29547284 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Inosine monophosphate dehydrogenase 3D structures

spinqualitylabelsall models 5ou2, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image