5cr5

X-RAY CRYSTAL STRUCTURE AT 1.61A RESOLUTION OF HUMAN MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE (BCATM) COMPLEXED WITH A BIPHENYL PYRROLIDINE ETHER COMPOUND AND AN INTERNAL ALDIMINE LINKED PLP COFACTOR.

spinqualitylabelsall models 5cr5, resolution 1.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cr5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.61Å Ligands: CL, DMS, EDO, EL1, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BCAT2_HUMAN Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids. Publication Abstract from PubMed As a potential target for obesity, human BCATm was screened against more than 14 billion DNA encoded compounds of distinct scaffolds followed by off-DNA synthesis and activity confirmation. As a consequence, several series of BCATm inhibitors were discovered. One representative compound (R)-3-((1-(5-bromothiophene-2-carbonyl)pyrrolidin-3-yl)oxy)-N-methyl-2'-(methylsu lfonamido)-[1,1'-biphenyl]-4-carboxamide (15e) from a novel compound library synthesized via on-DNA Suzuki-Miyaura cross-coupling showed BCATm inhibitory activity with IC50 = 2.0 muM. A protein crystal structure of 15e revealed that it binds to BCATm within the catalytic site adjacent to the PLP cofactor. The identification of this novel inhibitor series plus the establishment of a BCATm protein structure provided a good starting point for future structure-based discovery of BCATm inhibitors. Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA-Encoded Library.,Deng H, Zhou J, Sundersingh FS, Summerfield J, Somers D, Messer JA, Satz AL, Ancellin N, Arico-Muendel CC, Sargent Bedard KL, Beljean A, Belyanskaya SL, Bingham R, Smith SE, Boursier E, Carter P, Centrella PA, Clark MA, Chung CW, Davie CP, Delorey JL, Ding Y, Franklin GJ, Grady LC, Herry K, Hobbs C, Kollmann CS, Morgan BA, Pothier Kaushansky LJ, Zhou Q ACS Med Chem Lett. 2015 Jul 21;6(8):919-24. doi: 10.1021/acsmedchemlett.5b00179. , eCollection 2015 Aug 13. PMID:26288694 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminotransferase 3D structures

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