PDBsum entry: 1dqy

Immune system

PDB id: 1dqy

Contents

Protein chain

283 a.a. *

Ligands

DEP

MRD ×2

Waters ×292

* Residue conservation analysis

PDB id:

1dqy

Name:

Immune system

Title:

Crystal structure of antigen 85c from mycobacterium tuberculosis with diethyl phosphate inhibitor

Structure:

Protein (antigen 85-c). Chain: a. Synonym: 85c

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773

Resolution:

1.83Å R-factor: 0.168 R-free: 0.189

Authors:

D.R.Ronning,T.Klabunde,J.C.Sacchettini,Tb Structural Genomics Consortium (Tbsgc)

Key ref:

D.R.Ronning et al. (2000). Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines. Nat Struct Biol, 7, 141-146. PubMed id: 10655617 DOI: 10.1038/72413

Date:

05-Jan-00 Release date: 12-Jul-00

Protein chain

P0A4V4  (A85C_MYCTU) -  Antigen 85-C

Seq: 340 a.a.

Struc: 283 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: mycolate cell wall layer assembly (4 terms)
• Biochemical function: transferase activity (3 terms)

DOI no: 10.1038/72413

Nat Struct Biol 7:141-146 (2000)

PubMed id: 10655617

Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines.

D.R.Ronning, T.Klabunde, G.S.Besra, V.D.Vissa, J.T.Belisle, J.C.Sacchettini.

ABSTRACT

The antigen 85 (ag85) complex, composed of three proteins (ag85A, B and C), is a major protein component of the Mycobacterium tuberculosis cell wall. Each protein possesses a mycolyltransferase activity required for the biogenesis of trehalose dimycolate (cord factor), a dominant structure necessary for maintaining cell wall integrity. The crystal structure of recombinant ag85C from M. tuberculosis, refined to a resolution of 1.5 A, reveals an alpha/beta-hydrolase polypeptide fold, and a catalytic triad formed by Ser 124, Glu 228 and His 260. ag85C complexed with a covalent inhibitor implicates residues Leu 40 and Met 125 as components of the oxyanion hole. A hydrophobic pocket and tunnel extending 21 A into the core of the protein indicates the location of a probable trehalose monomycolate binding site. Also, a large region of conserved surface residues among ag85A, B and C is a probable site for the interaction of ag85 proteins with human fibronectin.

Selected figure(s)

Figure 1.
Figure 1. Structure of C chain of the secreted form of antigen 85C. a, Stereo diagram showing the C trace of apo-ag85C (residues 3 -282). b, Ribbon diagram of the C backbone of ag85. Residues of the catalytic triad Ser 124, His 260, Glu 228 are shown (carbon atoms are shown in white, oxygen atoms are red and nitrogen atoms are blue). The N and C termini of the resolved structure are labeled N and C, respectively. The figure was prepared with Setor40 c, 2F[o] - F[c] omit map of residues 122 -127 and DEP contoured at 1.5 . Carbon atoms are shown in white, oxygen atoms in red, nitrogen atoms in blue, phosphorus atom in orange and sulfur atom in yellow. Figure was made using Swiss PDB Viewer41 and rendered with POV-Ray42.

Figure 3.
Figure 3. Schematic representation of the catalytic mechanism of mycolyl transfer. In a three-step reaction, a mycolic acid, shown in red, is transferred from the 6-OH of one molecule of TMM to the 6'-OH of another TMM molecule, forming trehalose and TDM. Protein side chains are shown in black. The carbohydrate moiety of the substrate is in blue. The mycolic acid moiety is represented by a red or green R.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 141-146) copyright 2000.

Figures were selected by an automated process.