PDBsum entry: 1g95

Transferase

PDB id: 1g95

Contents

Protein chain

445 a.a. *

Waters ×276

* Residue conservation analysis

PDB id:

1g95

Name:

Transferase

Title:

Crystal structure of s.Pneumoniae glmu, apo form

Structure:

N-acetylglucosamine-1-phosphate uridyltransferase chain: a. Synonym: glmu, udp-n-acetylglucosamine pyrophosphorylase. Engineered: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Trimer (from PDB file)

Resolution:

2.33Å R-factor: 0.228 R-free: 0.303

Authors:

D.Kostrewa,A.D'Arcy,M.Kamber

Key ref:

D.Kostrewa et al. (2001). Crystal structures of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyltransferase, GlmU, in apo form at 2.33 A resolution and in complex with UDP-N-acetylglucosamine and Mg(2+) at 1.96 A resolution. J Mol Biol, 305, 279-289. PubMed id: 11124906 DOI: 10.1006/jmbi.2000.4296

Date:

22-Nov-00 Release date: 22-May-01

Protein chain

Q97R46  (GLMU_STRPN) -  Bifunctional protein GlmU

Seq: 459 a.a.

Struc: 445 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.3.1.157 - Glucosamine-1-phosphate N-acetyltransferase.
• Pathway: UDP-N-acetylglucosamine Biosynthesis
• Reaction: Acetyl-CoA + alpha-D-glucosamine 1-phosphate = CoA + N-acetyl-alpha-D- glucosamine 1-phosphate
• Enzyme class 2: E.C.2.7.7.23 - UDP-N-acetylglucosamine diphosphorylase.

Pathway:

• Reaction: UTP + N-acetyl-alpha-D-glucosamine 1-phosphate = diphosphate + UDP-N- acetyl-D-glucosamine

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: metabolic process (7 terms)
• Biochemical function: catalytic activity (8 terms)

reference

DOI no: 10.1006/jmbi.2000.4296

J Mol Biol 305:279-289 (2001)

PubMed id: 11124906

Crystal structures of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyltransferase, GlmU, in apo form at 2.33 A resolution and in complex with UDP-N-acetylglucosamine and Mg(2+) at 1.96 A resolution.

D.Kostrewa, A.D'Arcy, B.Takacs, M.Kamber.

ABSTRACT

N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential bacterial enzyme with both an acetyltransferase and a uridyltransferase activity which have been mapped to the C-terminal and N-terminal domains, respectively. GlmU performs the last two steps in the synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc), which is an essential precursor in both the peptidoglycan and the lipopolysaccharide metabolic pathways. GlmU is therefore an attractive target for potential antibiotics. Knowledge of its three-dimensional structure would provide a basis for rational drug design. We have determined the crystal structures of Streptococcus pneumoniae GlmU (SpGlmU) in apo form at 2.33 A resolution, and in complex with UDP-N-acetyl glucosamine and the essential co-factor Mg(2+) at 1.96 A resolution. The protein structure consists of an N-terminal domain with an alpha/beta-fold, containing the uridyltransferase active site, and a C-terminal domain with a long left-handed beta-sheet helix (LbetaH) domain. An insertion loop containing the highly conserved sequence motif Asn-Tyr-Asp-Gly protrudes from the left-handed beta-sheet helix domain. In the crystal, S. pneumoniae GlmU forms exact trimers, mainly through contacts between left-handed beta-sheet helix domains. UDP-N-acetylglucosamine and Mg(2+) are bound at the uridyltransferase active site, which is in a closed form. We propose a uridyltransferase mechanism in which the activation energy of the double negatively charged phosphorane transition state is lowered by charge compensation of Mg(2+) and the side-chain of Lys22.