1hn4

PROPHOSPHOLIPASE A2 DIMER COMPLEXED WITH MJ33, SULFATE, AND CALCIUM

spinqualitylabelsall models 1hn4, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1hn4 is a 2 chain structure with sequence from Pig. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, MJI, SO4 Activity: Phospholipase A(2), with EC number 3.1.1.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PA21B_PIG] PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Kinetic results in this paper show that, contrary to earlier reports, pig pancreatic prophospholipase A(2) (proPLA2) does not hydrolyze monodisperse short chain phosphatidylcholine below the critical micelle concentration. ProPLA2 is active on an anionic interface, but at a rate that is decreased by more than 100-fold compared to that of PLA2, the active form. Solution studies show that both proPLA2 and PLA2 bind to an anionic interface and also bind a tetrahedral intermediate mimic at the active site. The 1.5 A resolution crystal structure of the anion-assisted dimer of proPLA2 reported in this paper is compared with the corresponding structure for PLA2 [Pan, Y. H., et al. (2001) Biochemistry 40, 609-617]. As a mimic for the forms bound to the anionic interface, these structures provide insights into the possible structural basis for the impaired chemical step of the zymogen. The proPLA2 dimer contained within one crystallographic asymmetric unit has one molecule of the inhibitor 1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol and is bridged by four coplanar sulfate anions. Relative to the structure of PLA2, the subunit contact surface in proPLA2 displays a tilted orientation, an altered mode of inhibitor binding, displacement of a mechanistically significant loop that includes Tyr69, and a critical active site water seen in PLA2 that is not seen in proPLA2. These differences are interpreted to suggest possible origins of the functional differences between the pro and active enzyme at an anionic interface. A structural origin of this difference is discussed in terms of the calcium-coordinated activated water mechanism of the esterolysis reaction. Together, a comparison of the structures of the anion-assisted dimers of PLA2 and proPLA2 not only offers an explanation of why the zymogen form is k(cat)-impaired and binds poorly even to the anionic interface but also supports a mechanism for the activated enzyme that includes a critical second-sphere assisting water bridging His48 and the calcium-coordinated catalytic water. The basis for k(cat) impairment in prophospholipase A(2) from the anion-assisted dimer structure.,Epstein TM, Yu BZ, Pan YH, Tutton SP, Maliwal BP, Jain MK, Bahnson BJ Biochemistry. 2001 Sep 25;40(38):11411-22. PMID:11560489 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 3D structures

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