2vpq

Crystal structure of biotin carboxylase from S. aureus complexed with AMPPNP

spinqualitylabelsall models 2vpq, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vpq is a 2 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: ANP, CL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0H3JRR2_STAAM This protein is a component of the acetyl coenzyme A carboxylase complex; first, biotin carboxylase catalyzes the carboxylation of the carrier protein and then the transcarboxylase transfers the carboxyl group to form malonyl-CoA.[ARBA:ARBA00003761][RuleBase:RU365063] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Bacterial acetyl-CoA carboxylase is a multifunctional biotin-dependent enzyme that consists of three separate proteins: biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT). Acetyl-CoA carboxylase is a potentially attractive target for novel antibiotics because it catalyzes the first committed step in fatty acid biosynthesis. In the first half-reaction, BC catalyzes the ATP-dependent carboxylation of BCCP. In the second half-reaction, the carboxyl group is transferred from carboxybiotinylated BCCP to acetyl-CoA to produce malonyl-CoA. A series of structures of BC from several bacteria crystallized in the presence of various ATP analogs is described that addresses three major questions concerning the catalytic mechanism. The structure of BC bound to AMPPNP and the two catalytically essential magnesium ions resolves inconsistencies between the kinetics of active-site BC mutants and previously reported BC structures. Another structure of AMPPNP bound to BC shows the polyphosphate chain folded back on itself, and not in the correct (i.e., extended) conformation for catalysis. This provides the first structural evidence for the hypothesis of substrate-induced synergism, which posits that ATP binds nonproductively to BC in the absence of biotin. The BC homodimer has been proposed to exhibit half-sites reactivity where the active sites alternate or "flip-flop" their catalytic cycles. A crystal structure of BC showed the ATP analog AMPPCF(2)P bound to one subunit while the other subunit was unliganded. The liganded subunit was in the closed or catalytic conformation while the unliganded subunit was in the open conformation. This provides the first structural evidence for half-sites reactivity in BC. Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase.,Mochalkin I, Miller JR, Evdokimov A, Lightle S, Yan C, Stover CK, Waldrop GL Protein Sci. 2008 Oct;17(10):1706-18. Epub 2008 Aug 25. PMID:18725455 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetyl-CoA carboxylase 3D structures

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