2FAH
The structure of mitochondrial PEPCK, Complex with Mn and GDP
Summary for 2FAH
| Entry DOI | 10.2210/pdb2fah/pdb |
| Related | 2FAF 2FAG |
| Related PRD ID | PRD_900043 |
| Descriptor | Phosphoenolpyruvate carboxykinase, beta-D-fructofuranose-(2-1)-6-O-octanoyl-alpha-D-glucopyranose, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total) |
| Functional Keywords | phosphoenolpyruvate carboxykinase, pepck, pck, pep, gdp, kinase, phosphoryl transfer, lyase |
| Biological source | Gallus gallus (chicken) |
| Total number of polymer chains | 4 |
| Total formula weight | 273237.13 |
| Authors | Holyoak, T.,Sullivan, S.M.,Nowak, T. (deposition date: 2005-12-07, release date: 2006-06-27, Last modification date: 2023-08-30) |
| Primary citation | Holyoak, T.,Sullivan, S.M.,Nowak, T. Structural Insights into the Mechanism of PEPCK Catalysis Biochemistry, 45:8254-8263, 2006 Cited by PubMed Abstract: 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. PubMed: 16819824DOI: 10.1021/bi060269g PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.09 Å) |
Structure validation
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