5JAL
Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered Through X-Ray Fragment Screening
Summary for 5JAL
| Entry DOI | 10.2210/pdb5jal/pdb |
| Descriptor | Platelet-activating factor acetylhydrolase, MAGNESIUM ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | phospholipase, lipid metabolism, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 44567.68 |
| Authors | Day, P.J. (deposition date: 2016-04-12, release date: 2016-05-25, Last modification date: 2024-05-08) |
| Primary citation | Woolford, A.J.,Pero, J.E.,Aravapalli, S.,Berdini, V.,Coyle, J.E.,Day, P.J.,Dodson, A.M.,Grondin, P.,Holding, F.P.,Lee, L.Y.,Li, P.,Manas, E.S.,Marino, J.,Martin, A.C.,McCleland, B.W.,McMenamin, R.L.,Murray, C.W.,Neipp, C.E.,Page, L.W.,Patel, V.K.,Potvain, F.,Rich, S.,Rivero, R.A.,Smith, K.,Somers, D.O.,Trottet, L.,Velagaleti, R.,Williams, G.,Xie, R. Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening. J.Med.Chem., 59:5356-5367, 2016 Cited by PubMed Abstract: Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 Å from the catalytic residue Ser273). Using structure guided design, we optimized a fragment that bound in this pocket to generate a novel low nanomolar chemotype, which did not interact with the catalytic residues. PubMed: 27167608DOI: 10.1021/acs.jmedchem.6b00212 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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