4jem

Crystal structure of MilB complexed with cytidine 5'-monophosphate

spinqualitylabelsall models 4jem, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jem is a 2 chain structure with sequence from Streptomyces rimofaciens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.553Å Ligands: C5P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B4Y381_9ACTN Publication Abstract from PubMed MilB is a CMP hydrolase involved in the early steps of biosynthesis of the antifungal compound mildiomycin. An enzyme from the bacimethrin biosynthetic pathway, BcmB, is closely related to MilB in both sequence and function. These two enzymes belong to the nucleoside 2'-deoxyribosyltransferase (NDT) superfamily. NDTs catalyze N-glycosidic bond cleavage of 2'-deoxynucleosides via a covalent 2-deoxyribosyl-enzyme intermediate. Conservation of key active site residues suggests that members of the NDT superfamily share a common mechanism; however, the enzymes differ in their substrate preferences. Substrates vary in the type of nucleobase, the presence or absence of a 2'-hydroxyl group, and the presence or absence of a 5'-phosphate group. We have determined the structures of MilB and BcmB and compared them to previously determined structures of NDT superfamily members. The comparisons reveal how these enzymes differentiate between ribosyl and deoxyribosyl nucleotides or nucleosides and among different nucleobases. The 1.6 A structure of the MilB-CMP complex reveals an active site feature that is not obvious from comparisons of sequence alone. MilB and BcmB that prefer substrates containing 2'-ribosyl groups have a phenylalanine positioned in the active site, whereas NDT family members with a preference for 2'-deoxyribosyl groups have a tyrosine residue. Further studies show that the phenylalanine is critical for the specificity of MilB and BcmB toward CMP, and mutation of this phenylalanine residue to tyrosine results in a 1000-fold reversal of substrate specificity from CMP to dCMP. Reversal of the substrate specificity of CMP N-glycosidase to dCMP.,Sikowitz MD, Cooper LE, Begley TP, Kaminski PA, Ealick SE Biochemistry. 2013 Jun 11;52(23):4037-47. doi: 10.1021/bi400316p. Epub 2013 May, 28. PMID:23659472 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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