6ouw

1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Deinococcus radiodurans with enamine intermediate bound

spinqualitylabelsall models 6ouw, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ouw is a 1 chain structure with sequence from Deinococcus radiodurans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.398Å Ligands: HTL, MG, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DXS_DEIRA Catalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP) (By similarity).[HAMAP-Rule:MF_00315] Publication Abstract from PubMed 1-Deoxy-D-xylulose 5-phosphate synthase (DXPS) uses thiamine diphosphate (ThDP) to convert pyruvate and D-glyceraldehyde 3phosphate (D-GAP) into 1-deoxy-D-xylulose 5-phosphate (DXP), an essential bacterial metabolite. DXP is not utilized by humans; hence, DXPS has been an attractive antibacterial target. Here, we investigate DXPS from Deinococcus radiodurans (DrDXPS), showing that it has similar kinetic parameters Km (d-GAP )and Km (pyruvate )(54 +/- 3 microM and 11 +/- 1 microM, respectively) and comparable catalytic activity (k cat = 45 +/- 2 min(-1)) to previously studied bacterial DXPS enzymes, and employing it to obtain missing structural data on this enzyme family. In particular, we have determined crystallographic snapshots of DrDXPS in two states along the reaction coordinate - a structure of DrDXPS bound to C2alpha-phosphonolactylThDP (PLThDP), mimicking the native pre-decarboxylation intermediate C2alpha-lactylThDP (LThDP), and a native post-decarboxylation state with a bound enamine intermediate. The 1.94-A resolution structure of PLThDP-bound DrDXPS delineates how two active site histidine residues stabilize the LThDP intermediate. Meanwhile, the 2.40-A resolution structure of an enamine intermediate-bound DrDXPS reveals how a previously unknown 17-A conformational change removes one of the two histidine residues from the active site, likely triggering LThDP decarboxylation to form the enamine intermediate. These results provide insight into how the bi-substrate enzyme DXPS limits side reactions by arresting the reaction on the less reactive LThDP intermediate when its co-substrate is absent. They also offer a molecular basis for previous low-resolution experimental observations that correlate decarboxylation of LThDP with protein conformational changes. X-ray crystallography-based structural elucidation of enzyme-bound intermediates along the 1deoxydxylulose 5-phosphate synthase reaction coordinate.,Chen PY, DeColli AA, Freel Meyers CL, Drennan CL J Biol Chem. 2019 Jun 25. pii: RA119.009321. doi: 10.1074/jbc.RA119.009321. PMID:31239351 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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