2qzy

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Revision as of 11:49, 21 November 2007

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spinqualitylabelsall models 2qzy, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The structure of chicken mitochondrial PEPCK in complex with PEP

Overview

Phosphoenolpyruvate carboxykinase catalyzes the reversible decarboxylation, of oxaloacetic acid with the concomitant transfer of the gamma-phosphate, of GTP to form PEP and GDP as the first committed step of gluconeogenesis, and glyceroneogenesis. The three structures of the mitochondrial isoform, of PEPCK reported are complexed with Mn2+, Mn2+-PEP, or Mn2+-malonate-Mn2+, GDP and provide the first observations of the structure of the, mitochondrial isoform and insight into the mechanism of catalysis mediated, by this enzyme. The structures show the involvement of the hyper-reactive, cysteine (C307) in the coordination of the active site Mn2+. Upon, formation of the PEPCK-Mn2+-PEP or PEPCK-Mn2+-malonate-Mn2+ GDP complexes, C307 coordination is lost as the P-loop in which it resides adopts a, different conformation. The structures suggest that stabilization of the, cysteine-coordinated metal geometry holds the enzyme as a catalytically, incompetent metal complex and may represent a previously unappreciated, mechanism of regulation. A third conformation of the mobile P-loop in the, PEPCK-Mn2+-malonate-Mn2+ GDP complex demonstrates the participation of a, previously unrecognized, conserved serine residue (S305) in mediating, phosphoryl transfer. The ordering of the mobile active site lid in the, PEPCK-Mn2+-malonate-Mn2+ GDP complex yields the first observation of this, structural feature and provides additional insight into the mechanism of, phosphoryl transfer.

About this Structure

2QZY is a Single protein structure of sequence from Gallus gallus with MN, PEP, EPE and 20S as ligands. This structure superseeds the now removed PDB entry 2FAG. Active as Phosphoenolpyruvate carboxykinase (GTP), with EC number 4.1.1.32 Full crystallographic information is available from OCA.

Reference

Structural insights into the mechanism of PEPCK catalysis., Holyoak T, Sullivan SM, Nowak T, Biochemistry. 2006 Jul 11;45(27):8254-63. PMID:16819824

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