Structural highlights
Function
[GLMU_ECOLI] 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.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) is a cytoplasmic bifunctional enzyme involved in the biosynthesis of the nucleotide-activated UDP-GlcNAc, which is an essential precursor for the biosynthetic pathways of peptidoglycan and other components in bacteria. The crystal structure of a truncated form of GlmU has been solved at 2.25 A resolution using the multiwavelength anomalous dispersion technique and its function tested with mutagenesis studies. The molecule is composed of two distinct domains connected by a long alpha-helical arm: (i) an N-terminal domain which resembles the dinucleotide-binding Rossmann fold; and (ii) a C-terminal domain which adopts a left-handed parallel beta-helix structure (LbetaH) as found in homologous bacterial acetyltransferases. Three GlmU molecules assemble into a trimeric arrangement with tightly packed parallel LbetaH domains, the long alpha-helical linkers being seated on top of the arrangement and the N-terminal domains projected away from the 3-fold axis. In addition, the 2.3 A resolution structure of the GlmU-UDP-GlcNAc complex reveals the structural bases required for the uridyltransferase activity. These structures exemplify a three-dimensional template for the development of new antibacterial agents and for studying other members of the large family of XDP-sugar bacterial pyrophosphorylases.
Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily.,Brown K, Pompeo F, Dixon S, Mengin-Lecreulx D, Cambillau C, Bourne Y EMBO J. 1999 Aug 2;18(15):4096-107. PMID:10428949[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mengin-Lecreulx D, van Heijenoort J. Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis. J Bacteriol. 1994 Sep;176(18):5788-95. PMID:8083170
- ↑ Gehring AM, Lees WJ, Mindiola DJ, Walsh CT, Brown ED. Acetyltransfer precedes uridylyltransfer in the formation of UDP-N-acetylglucosamine in separable active sites of the bifunctional GlmU protein of Escherichia coli. Biochemistry. 1996 Jan 16;35(2):579-85. PMID:8555230 doi:http://dx.doi.org/10.1021/bi952275a
- ↑ Brown K, Pompeo F, Dixon S, Mengin-Lecreulx D, Cambillau C, Bourne Y. Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily. EMBO J. 1999 Aug 2;18(15):4096-107. PMID:10428949 doi:10.1093/emboj/18.15.4096
