1hn4

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spinqualitylabelsall models 1hn4, resolution 1.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

PROPHOSPHOLIPASE A2 DIMER COMPLEXED WITH MJ33, SULFATE, AND CALCIUM

Overview

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.

About this Structure

1HN4 is a Single protein structure of sequence from Sus scrofa with CA, SO4 and MJI as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.

Reference

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

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