4gnm

Structure of rat cytosolic PEPCK Ld_2g in complex with oxalate and GTP

spinqualitylabelsall models 4gnm, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gnm is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GTP, MN, NA, OXL Related: 4gmm, 4gmu, 4gmw, 4gmz, 4gnl, 4gno, 4gnp, 4gnq Gene: Pck1 (Buffalo rat) Activity: Phosphoenolpyruvate carboxykinase (GTP), with EC number 4.1.1.32 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PCKGC_RAT] Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Publication Abstract from PubMed Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Recent studies have demonstrated that the enzyme contains a mobile active site lid domain that undergoes a transition between an open, disorded conformation and a closed, ordered conformation as the enzyme progresses through the catalytic cycle. The understanding of how this mobile domain functions in catalysis is incomplete. Previous studies showed that the closure of the lid domain stabilizes the reaction intermediate and protects the reactive intermediate from spurious protonation and thus contributes to the fidelity of the enzyme. To more fully investigate the roles of the lid domain in PEPCK function, we introduced three mutations that replaced the 11-residue lid domain with one, two, and three glycine residues. Kinetic analysis of the mutant enzymes demonstrates that none of the enzyme constructs exhibit any measurable kinetic activity, resulting in a decrease in the catalytic parameters of at least 10(6). Structural characterization of the mutants in complexes representing the catalytic cycle suggests that the inactivity is due to a role for the lid domain in the formation of the fully closed state of the enzyme that is required for catalytic function. In the absence of the lid domain, the enzyme is unable to achieve the fully closed state and is rendered inactive despite possessing all of the residues and substrates required for catalytic function. This work demonstrates how enzyme catalytic function can be abolished through the alteration of conformational equilibria despite all the elements required for chemical conversion of substrates to products remaining intact. The Omega-loop lid domain of phosphoenolpyruvate carboxykinase is essential for catalytic function.,Johnson TA, Holyoak T Biochemistry. 2012 Nov 27;51(47):9547-59. doi: 10.1021/bi301278t. Epub 2012 Nov, 14. PMID:23127136 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA