5KRE
Covalent inhibitor of LYPLAL1
Summary for 5KRE
| Entry DOI | 10.2210/pdb5kre/pdb |
| Descriptor | Lysophospholipase-like protein 1, (2~{R})-2-phenylpiperidine-1-carbaldehyde, NITRATE ION, ... (4 entities in total) |
| Functional Keywords | lyplal1, serine hydrolase, covalent inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Isoform 1: Cytoplasm, cytosol . Isoform 2: Cytoplasm, cytosol : Q5VWZ2 |
| Total number of polymer chains | 1 |
| Total formula weight | 26772.90 |
| Authors | Pandit, J. (deposition date: 2016-07-07, release date: 2016-07-20, Last modification date: 2024-11-06) |
| Primary citation | Ahn, K.,Boehm, M.,Brown, M.F.,Calloway, J.,Che, Y.,Chen, J.,Fennell, K.F.,Geoghegan, K.F.,Gilbert, A.M.,Gutierrez, J.A.,Kalgutkar, A.S.,Lanba, A.,Limberakis, C.,Magee, T.V.,O'Doherty, I.,Oliver, R.,Pabst, B.,Pandit, J.,Parris, K.,Pfefferkorn, J.A.,Rolph, T.P.,Patel, R.,Schuff, B.,Shanmugasundaram, V.,Starr, J.T.,Varghese, A.H.,Vera, N.B.,Vernochet, C.,Yan, J. Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism. Acs Chem.Biol., 11:2529-2540, 2016 Cited by PubMed Abstract: Lysophospholipase-like 1 (LYPLAL1) is an uncharacterized metabolic serine hydrolase. Human genome-wide association studies link variants of the gene encoding this enzyme to fat distribution, waist-to-hip ratio, and nonalcoholic fatty liver disease. We describe the discovery of potent and selective covalent small-molecule inhibitors of LYPLAL1 and their use to investigate its role in hepatic metabolism. In hepatocytes, selective inhibition of LYPLAL1 increased glucose production supporting the inference that LYPLAL1 is a significant actor in hepatic metabolism. The results provide an example of how a selective chemical tool can contribute to evaluating a hypothetical target for therapeutic intervention, even in the absence of complete biochemical characterization. PubMed: 27391855DOI: 10.1021/acschembio.6b00266 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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