PDBsum entry 2dkc

Isomerase

PDB id: 2dkc

Contents

Protein chains

536 a.a. *

Ligands

16G ×2

PO4 ×2

Metals

_ZN ×2

Waters ×647

* Residue conservation analysis

PDB id:

2dkc

Name:

Isomerase

Title:

Crystal structure of n-acetylglucosamine-phosphate mutase, a member of the alpha-d-phosphohexomutase superfamily, in the substrate complex

Structure:

Phosphoacetylglucosamine mutase. Chain: a, b. Synonym: pagm, acetylglucosamine phosphomutase, n-acetylglucosamine- phosphate mutase. Engineered: yes

Source:

Candida albicans. Organism_taxid: 5476. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.189 R-free: 0.240

Authors:

Y.Nishitani,D.Maruyama,T.Nonaka,A.Kita,T.A.Fukami,T.Mio,H.Yamada- Okabe,T.Yamada-Okabe,K.Miki

Key ref:

Y.Nishitani et al. (2006). Crystal structures of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, and its substrate and product complexes. J Biol Chem, 281, 19740-19747. PubMed id: 16651269 DOI: 10.1074/jbc.M600801200

Date:

07-Apr-06 Release date: 16-May-06

Protein chains

Q9P4V2  (AGM1_CANAX) -  Phosphoacetylglucosamine mutase from Candida albicans

Seq: 544 a.a.

Struc: 536 a.a.

Enzyme reactions

• Enzyme class: E.C.5.4.2.3 - phosphoacetylglucosamine mutase.
• Pathway: UDP-N-acetylglucosamine Biosynthesis
• Reaction: N-acetyl-alpha-D-glucosamine 1-phosphate = N-acetyl-D-glucosamine 6-phosphate

N-acetyl-alpha-D-glucosamine 1-phosphate = N-acetyl-D-glucosamine 6-phosphate (Bound ligand (Het Group name = 16G) corresponds exactly)

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

Added reference

DOI no: 10.1074/jbc.M600801200

J Biol Chem 281:19740-19747 (2006)

PubMed id: 16651269

Crystal structures of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, and its substrate and product complexes.

Y.Nishitani, D.Maruyama, T.Nonaka, A.Kita, T.A.Fukami, T.Mio, H.Yamada-Okabe, T.Yamada-Okabe, K.Miki.

ABSTRACT

N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the synthetic process of UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a UDP sugar that serves as a biosynthetic precursor of glycoproteins, mucopolysaccharides, and the cell wall of bacteria. Thus, a specific inhibitor of AGM1 from pathogenetic fungi could be a new candidate for an antifungal reagent that inhibits cell wall synthesis. AGM1 catalyzes the conversion of N-acetylglucosamine 6-phosphate (GlcNAc-6-P) into N-acetylglucosamine 1-phosphate (GlcNAc-1-P). This enzyme is a member of the alpha-D-phosphohexomutase superfamily, which catalyzes the intramolecular phosphoryl transfer of sugar substrates. Here we report the crystal structures of AGM1 from Candida albicans for the first time, both in the apoform and in the complex forms with the substrate and the product, and discuss its catalytic mechanism. The structure of AGM1 consists of four domains, of which three domains have essentially the same fold. The overall structure is similar to those of phosphohexomutases; however, there are two additional beta-strands in domain 4, and a circular permutation occurs in domain 1. The catalytic cleft is formed by four loops from each domain. The N-acetyl group of the substrate is recognized by Val-370 and Asn-389 in domain 3, from which the substrate specificity arises. By comparing the substrate and product complexes, it is suggested that the substrate rotates about 180 degrees on the axis linking C-4 and the midpoint of the C-5-O-5 bond in the reaction.

Selected figure(s)

Figure 1.
Schematic illustration of the role of AGM1 in the biosynthetic pathway of UDP-GlcNAc. In eukaryotes, UDP-GlcNAc is synthesized from fructose 6-phosphate by four successive reactions: (i) the conversion of Fru-6-P into GlcN-6-P; (ii) the acetylation of GlcN-6-P into GlcNAc-6-P; (iii) the interconversion of GlcNAc-6-P and GlcNAc-1-P; and (iv) the uridylation of GlcNAc-1-P into UDP-GlcNAc. AGM1 is catalyzed in step iii.In prokaryotes, the intramolecular phosphoryl transfer (step iii) occurs before acetylation (step ii), and GlcN-1-P is generated as the intermediate.

Figure 8.
Schematic drawing of the proposed catalytic mechanism for the conversion of GlcNAc-6-P to GlcNAc-1-P by AGM1. Phosphoryl groups are indicated by P in a shaded circle. The phosphoryl group near Ser-66 first binds to the substrate. The substrate is converted into a bis-phosphorylated intermediate. Then, this intermediate rotates at 180°. Consequently, the phosphoryl group at C-6 changes positions with another phosphoryl group at C-1. Finally, the phosphoryl group moved near the metal ion dissociates from the intermediate and binds to Ser-66.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 19740-19747) copyright 2006.

Figures were selected by an automated process.