Application | Comment | Organism |
---|---|---|
drug development | prokaryotic/microbial sugar nucleotidyl transferases are targets for design of selective inhibitors due to their different metal mechanisms compared to eukaryotes | Mycobacterium tuberculosis |
Crystallization (Comment) | Organism |
---|---|
GlmUMtb active site crystal structure analysis, PDB ID 3DJ4, and crystal structure of GlmU with both substrates (i.e., GlcNAc-1-P and UTP) in the presence of metal ions, soaking of GlmUMtb[Apo] crystals in a solution containing GlcNAc-1-P, UTP and MgCl2. the soaking solution consists of 10% PEG 8000, 100 mM HEPES, pH 7.5, 20 mM MgCl2, and 4 mM CoCl2, and substrate 50 mM GlcNAc-1-phosphate, with or without 10 mM UTP, for 4 h at 4°C, X-ray diffraction structure determination and analysis at 2.0 A resolution using molecular replacement with GlmUMtb[Apo] as a search model | Mycobacterium tuberculosis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Co2+ | a cobalt ion substitutes for Mg2+A in the crystal structure | Mycobacterium tuberculosis | |
Mg2+ | required, two metal binding sites, site-A and site-B. The enzyme uses a two-metal ion mechanism (mechanism-B). Roles of the metal ions in substrate stabilization, nucleophile activation and transition-state stabilization, detailed overview. Mg2+A interacts with Asp114 and Asn239 and oxygens O1B and O2A of UDP-GlcNAc in addition to two water molecules. Mg2+B is coordinated with three water molecules and the oxygen atoms are contributed by UDP-GlcNAc and diphosphate. Mg2+A enables nucleophile activation and Mg2+B stabilizes the transition state | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate | Mycobacterium tuberculosis | - |
diphosphate + UDP-N-acetyl-alpha-D-glucosamine | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | P9WMN3 | - |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate = diphosphate + UDP-N-acetyl-alpha-D-glucosamine | catalytic mechanism for the uridyltransfer reaction in the bifunctional enzyme GlmU, overview. The enzyme has distinct roles for Mg2+A and Mg2+B in substrate stabilization, nucleophile activation and transition-state stabilization | Mycobacterium tuberculosis |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
Mycobacterium tuberculosis | diphosphate + UDP-N-acetyl-alpha-D-glucosamine | - |
r |
Subunits | Comment | Organism |
---|---|---|
trimer | GlmU forms a biological trimer, and two independent domains in each monomer catalyze two independent reactions in the protein | Mycobacterium tuberculosis |
Synonyms | Comment | Organism |
---|---|---|
GlmU | - |
Mycobacterium tuberculosis |
N-acetylglucosamine-1-phosphate uridyltransferase | - |
Mycobacterium tuberculosis |
General Information | Comment | Organism |
---|---|---|
evolution | GlmU belongs to the large family of sugar nucleotidyl transferases, which can 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 Mg2+ A is substituted by a conserved lysine. Eukaryotic sugar nucleotidyl transferases appear confined to group-II, structure-based sequence comparisons of sugar nucleotidyl transferases | Mycobacterium tuberculosis |
additional information | GlmU forms a biological trimer, and two independent domains in each monomer catalyze two independent reactions in the protein. The enzyme uses 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 Mg2+ ions (Mg2+A and Mg2+B) are positioned and stabilized. Analysis of the catalytic mechanism for the uridyltransfer reaction in GlmU, role of metal ions in substrate binding, overview | Mycobacterium tuberculosis |
physiological function | N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is exclusive to prokaryotes and a bifunctional enzyme that synthesizes UDP-GlcNAc, an important component of the cell wall of many microorganisms | Mycobacterium tuberculosis |