4mfd

Structure of the carboxyl transferase domain from Rhizobium etli pyruvate carboxylase with oxalate

spinqualitylabelsall models 4mfd, resolution 2.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mfd is a 4 chain structure with sequence from Rhizobium etli CFN 42. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.55Å Ligands: CL, GOL, KCX, MG, OXL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2K340_RHIEC Catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second (By similarity).[PIRNR:PIRNR001594] Publication Abstract from PubMed Pyruvate carboxylase (PC) is a biotin-dependent enzyme that catalyzes the MgATP- and bicarbonate-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in central metabolism. The carboxyltransferase (CT) domain of PC catalyzes the transfer of a carboxyl group from carboxybiotin to the accepting substrate, pyruvate. It has been hypothesized that the reactive enolpyruvate intermediate is stabilized through a bidentate interaction with the metal ion in the CT domain active site. Whereas bidentate ligands are commonly observed in enzymes catalyzing reactions proceeding through an enolpyruvate intermediate, no bidentate interaction has yet been observed in the CT domain of PC. Here, we report three X-ray crystal structures of the Rhizobium etli PC CT domain with the bound inhibitors oxalate, 3-hydroxypyruvate, and 3-bromopyruvate. Oxalate, a stereoelectronic mimic of the enolpyruvate intermediate, does not interact directly with the metal ion. Instead, oxalate is buried in a pocket formed by several positively charged amino acid residues and the metal ion. Furthermore, both 3-hydroxypyruvate and 3-bromopyruvate, analogs of the reaction product oxaloacetate, bind in an identical manner to oxalate suggesting that the substrate maintains its orientation in the active site throughout catalysis. Together, these structures indicate that the substrates, products and intermediates in the PC-catalyzed reaction are not oriented in the active site as previously assumed. The absence of a bidentate interaction with the active site metal appears to be a unique mechanistic feature among the small group of biotin-dependent enzymes that act on alpha-keto acid substrates. Insights into the carboxyltransferase reaction of pyruvate carboxylase from the structures of bound product and intermediate analogs.,Lietzan AD, St Maurice M Biochem Biophys Res Commun. 2013 Oct 22. pii: S0006-291X(13)01738-5. doi:, 10.1016/j.bbrc.2013.10.066. PMID:24157795 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyruvate carboxylase 3D structures

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