6MTW
Lysosomal Phospholipase A2 in complex with Zinc
Summary for 6MTW
| Entry DOI | 10.2210/pdb6mtw/pdb |
| Descriptor | Group XV phospholipase A2, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | lipase, esterase, hydrolase, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 87721.06 |
| Authors | Bouley, R.,Tesmer, J.J.G. (deposition date: 2018-10-22, release date: 2019-03-20, Last modification date: 2024-11-13) |
| Primary citation | Bouley, R.A.,Hinkovska-Galcheva, V.,Shayman, J.A.,Tesmer, J.J.G. Structural Basis of Lysosomal Phospholipase A2Inhibition by Zn2. Biochemistry, 58:1709-1717, 2019 Cited by PubMed Abstract: Lysosomal phospholipase A (LPLA/PLA2G15) is a key enzyme involved in lipid homeostasis and is characterized by both phospholipase A2 and transacylase activity and by an acidic pH optimum. Divalent cations such as Ca and Mg have previously been shown to have little effect on the activity of LPLA, but the discovery of a novel crystal form of LPLA with Zn bound in the active site suggested a role for this divalent cation in regulating enzyme activity. In this complex, the cation directly coordinates the serine and histidine of the α/β-hydrolase triad and stabilizes a closed conformation. This closed conformation is characterized by an inward shift of the lid loop, which extends over the active site and effectively blocks access to one of its lipid acyl chain binding tracks. Therefore, we hypothesized that Zn would inhibit LPLA activity at a neutral but not acidic pH because histidine would be positively charged at lower pH. Indeed, Zn was found to inhibit the esterase activity of LPLA in a noncompetitive manner exclusively at a neutral pH (between 6.5 and 8.0). Because lysosomes are reservoirs of Zn in cells, the pH optimum of LPLA might allow it to catalyze acyl transfer unimpeded within the organelle. We conjecture that Zn inhibition of LPLA at higher pH maintains a lower activity of the esterase in environments where its activity is not typically required. PubMed: 30830753DOI: 10.1021/acs.biochem.8b01124 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.999 Å) |
Structure validation
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