4hcq

Crystal structure of GLMU from mycobacterium tuberculosis in complex with glucosamine-1-phosphate

spinqualitylabelsall models 4hcq, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hcq is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: CO, GN1, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLMU_MYCTU Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain. Publication Abstract from PubMed N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU), exclusive to prokaryotes, is a bifunctional enzyme that synthesizes UDP-GlcNAc-an important component of the cell wall of many microorganisms. Uridyltransfer, one of the reactions it catalyzes, involves binding GlcNAc-1-P, UTP and Mg(2+) ions; however, whether one or two ions catalyze this reaction remains ambiguous. Here, we resolve this using biochemical and crystallographic studies on GlmU from Mycobacterium tuberculosis (GlmU(Mtb)) and identify a two-metal-ion mechanism (mechanism-B). In contrast to well-established two-metal mechanism (mechanism-A) for enzymes acting on nucleic acids, mechanism-B is distinct in the way the two Mg(2+) ions (Mg(2+)A and Mg(2+)B) are positioned and stabilized. Further, attempts to delineate the roles of the metal ions in substrate stabilization, nucleophile activation and transition-state stabilization are presented. Interestingly, a detailed analysis of the available structures of sugar nucleotidyl transferases (SNTs) suggests that they too would utilize mechanism-B rather than mechanism-A. Based on this, SNTs could be classified into Group-I, which employs the two-metal mechanism-B as in GlmU, and Group-II that employs a variant one-metal mechanism-B, wherein the role of Mg(2+)A is substituted by a conserved lysine. Strikingly, eukaryotic SNTs appear confined to Group-II. Recognizing these differences may be important in the design of selective inhibitors against microbial nucleotidyl transferases. Crystal structures identify an atypical two-metal-ion mechanism for uridyltransfer in GlmU: its significance to sugar nucleotidyl transferases.,Jagtap PK, Verma SK, Vithani N, Bais VS, Prakash B J Mol Biol. 2013 May 27;425(10):1745-59. doi: 10.1016/j.jmb.2013.02.019. Epub, 2013 Feb 26. PMID:23485416 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also N-acetylglucosamine-1-phosphate uridyltransferase

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