PDBsum entry 3d8v

Transferase

PDB id: 3d8v

Contents

Protein chain

478 a.a. *

Ligands

UD1

Waters ×147

* Residue conservation analysis

PDB id:

3d8v

Name:

Transferase

Title:

Crystal structure of glmu from mycobacterium tuberculosis in complex with uridine-diphosphate-n-acetylglucosamine

Structure:

Bifunctional protein glmu. Chain: a. Synonym: [includes: udp-n-acetylglucosamine pyrophosphorylase (ec 2.7.7.23) (n-acetylglucosamine-1-phosphate uridyltransferase). Glucosamine-1-phosphate n-acetyltransferase (ec 2.3.1.157)]. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: glmu, rv1018c, mt1046. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.55Å R-factor: 0.201 R-free: 0.244

Authors:

Z.Zhang,C.J.Squire,E.N.Baker

Key ref:

Z.Zhang et al. (2009). Structure and function of GlmU from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr, 65, 275-283. PubMed id: 19237750 DOI: 10.1107/S0907444909001036

Date:

25-May-08 Release date: 10-Mar-09

Protein chain

P9WMN3  (GLMU_MYCTU) -  Bifunctional protein GlmU from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 495 a.a.

Struc: 478 a.a.

Enzyme reactions

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

alpha-D-glucosamine 1-phosphate + acetyl-CoA = N-acetyl-alpha-D- glucosamine 1-phosphate (Bound ligand (Het Group name = UD1) matches with 50.00% similarity) + CoA + H(+)

• Enzyme class 2: E.C.2.7.7.23 - UDP-N-acetylglucosamine diphosphorylase.

Pathway:

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

N-acetyl-alpha-D-glucosamine 1-phosphate + UTP + H(+) (Bound ligand (Het Group name = UD1) matches with 58.14% similarity) = UDP-N-acetyl- alpha-D-glucosamine + diphosphate

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

reference

DOI no: 10.1107/S0907444909001036

Acta Crystallogr D Biol Crystallogr 65:275-283 (2009)

PubMed id: 19237750

Structure and function of GlmU from Mycobacterium tuberculosis.

Z.Zhang, E.M.Bulloch, R.D.Bunker, E.N.Baker, C.J.Squire.

ABSTRACT

Antibiotic resistance is a major issue in the treatment of infectious diseases such as tuberculosis. Existing antibiotics target only a few cellular pathways and there is an urgent need for antibiotics that have novel molecular mechanisms. The glmU gene is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth, and has been selected as a possible drug target for structural and functional investigation. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathways: lipopolysaccharide and peptidoglycan synthesis. The crystal structure of M. tuberculosis GlmU has been determined in an unliganded form and in complex with GlcNAc-1-P or UDP-GlcNAc. The structures reveal the residues that are responsible for substrate binding. Enzyme activities were characterized by (1)H NMR and suggest that the presence of acetyl-coenzyme A has an inhibitory effect on uridyltransferase activity.

Selected figure(s)

Figure 3.
Figure 3 The uridyltransferase active site. (a) Binding of GlcNAc-1-P (ball-and-stick model). Hydrogen bonds are shown as dashed lines and the 2F[o] - F[c] electron density is contoured at 1.0 . (b) Comparison of GlcNAc-1-P (white outlined protein) and UDP-GlcNAc (blue protein) binding and associated loop movement within the uracil site. GlcNAc-1-P and UDP-GlcNAc molecules are drawn as ball-and-stick models with white- and yellow-coloured C atoms, respectively. Water molecules are drawn as red spheres and are associated with the UDP-GlcNAc protein model.

The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2009, 65, 275-283) copyright 2009.

Figure was selected by the author.