3upl

Crystal structure of the Brucella abortus enzyme catalyzing the first committed step of the methylerythritol 4-phosphate pathway.

spinqualitylabelsall models 3upl, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3upl is a 2 chain structure with sequence from Brucella abortus and Brucella melitensis biovar abortus 2308. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MG Related: 3upy Gene: BAB2_0264, DRL (Brucella melitensis biovar Abortus 2308), DRL (Brucella abortus) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Most bacteria use the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the synthesis of their essential isoprenoid precursors. The absence of the MEP pathway in humans makes it a promising new target for the development of much needed new and safe antimicrobial drugs. However, bacteria show a remarkable metabolic plasticity for isoprenoid production. For example, the NADPH-dependent production of MEP from 1-deoxy-D-xylulose 5-phosphate in the first committed step of the MEP pathway is catalyzed by 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in most bacteria, whereas an unrelated DXR-like (DRL) protein was recently found to catalyze the same reaction in some organisms, including the emerging human and animal pathogens Bartonella and Brucella. Here, we report the x-ray crystal structures of the Brucella abortus DRL enzyme in its apo form and in complex with the broad-spectrum antibiotic fosmidomycin solved to 1.5 and 1.8 A resolution, respectively. DRL is a dimer, with each polypeptide folding into three distinct domains starting with the NADPH-binding domain, in resemblance to the structure of bacterial DXR enzymes. Other than that, DRL and DXR show a low structural relationship, with a different disposition of the domains and a topologically unrelated C-terminal domain. In particular, the active site of DRL presents a unique arrangement, suggesting that the design of drugs that would selectively inhibit DRL-harboring pathogens without affecting beneficial or innocuous bacteria harboring DXR should be feasible. As a proof of concept, we identified two strong DXR inhibitors that have virtually no effect on DRL activity. Crystal structure of Brucella abortus deoxyxylulose-5-phosphate reductoisomerase-like (DRL) enzyme involved in isoprenoid biosynthesis.,Perez-Gil J, Calisto BM, Behrendt C, Kurz T, Fita I, Rodriguez-Concepcion M J Biol Chem. 2012 May 4;287(19):15803-9. Epub 2012 Mar 22. PMID:22442144 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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