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7ny2

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CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC BRANCHED-CHAIN AMINOTRANSFERASE (BCAT1) IN COMPLEX WITH PLP AND SMALL MOLECULE INHIBITOR COMPOUND 35

Structural highlights

7ny2 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 2.31Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BCAT1_HUMAN Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.

Publication Abstract from PubMed

The branched-chain amino acid transaminases (BCATs) are enzymes that catalyze the first reaction of catabolism of the essential branched-chain amino acids to branched-chain keto acids to form glutamate. They are known to play a key role in different cancer types. Here, we report a new structural class of BCAT1/2 inhibitors, (trifluoromethyl)pyrimidinediones, identified by a high-throughput screening campaign and subsequent optimization guided by a series of X-ray crystal structures. Our potent dual BCAT1/2 inhibitor BAY-069 displays high cellular activity and very good selectivity. Along with a negative control (BAY-771), BAY-069 was donated as a chemical probe to the Structural Genomics Consortium.

BAY-069, a Novel (Trifluoromethyl)pyrimidinedione-Based BCAT1/2 Inhibitor and Chemical Probe.,Gunther J, Hillig RC, Zimmermann K, Kaulfuss S, Lemos C, Nguyen D, Rehwinkel H, Habgood M, Lechner C, Neuhaus R, Ganzer U, Drewes M, Chai J, Bouche L J Med Chem. 2022 Oct 19. doi: 10.1021/acs.jmedchem.2c00441. PMID:36261130^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gunther J, Hillig RC, Zimmermann K, Kaulfuss S, Lemos C, Nguyen D, Rehwinkel H, Habgood M, Lechner C, Neuhaus R, Ganzer U, Drewes M, Chai J, Bouche L. BAY-069, a Novel (Trifluoromethyl)pyrimidinedione-Based BCAT1/2 Inhibitor and Chemical Probe. J Med Chem. 2022 Oct 19. doi: 10.1021/acs.jmedchem.2c00441. PMID:36261130 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c00441