1f0n

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1f0n, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

MYCOBACTERIUM TUBERCULOSIS ANTIGEN 85B

Overview

The Mycobacterium tuberculosis 30 kDa major secretory protein (antigen, 85B) is the most abundant protein exported by M. tuberculosis, as well as, a potent immunoprotective antigen and a leading drug target. A mycolyl, transferase of 285 residues, it is closely related to two other mycolyl, transferases, each of molecular mass 32 kDa: antigen 85A and antigen 85C., All three catalyze transfer of the fatty acid mycolate from one trehalose, monomycolate to another, resulting in trehalose dimycolate and free, trehalose, thus helping to build the bacterial cell wall. We have, determined two crystal structures of M. tuberculosis antigen 85B (ag85B), initially by molecular replacement using antigen 85C as a probe. The apo, ag85B model is refined against 1.8 A data, to an R-factor of 0.196, (R(free) is 0.276), and includes all residues except the N-terminal Phe., The active site immobilizes a molecule of the cryoprotectant, 2-methyl-2,4-pentanediol. Crystal growth with addition of trehalose, resulted in a second ag85B crystal structure (1.9 A resolution; R-factor, is 0.195; R(free) is 0.285). Trehalose binds in two sites at opposite ends, of the active-site cleft. In our proposed mechanism model, the trehalose, at the active site Ser126 represents the trehalose liberated by temporary, esterification of Ser126, while the other trehalose represents the, incoming trehalose monomycolate just prior to swinging over to the first, trehalose site to displace the mycolate from its serine ester. Our, proposed interfacial mechanism minimizes aqueous exposure of the apolar, mycolates. Based on the trehalose-bound structure, we suggest a new class, of antituberculous drugs, made by connecting two trehalose molecules by an, amphipathic linker.

About this Structure

1F0N is a Single protein structure of sequence from Mycobacterium tuberculosis with MES and MPD as ligands. Full crystallographic information is available from OCA.

Reference

An interfacial mechanism and a class of inhibitors inferred from two crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory protein (Antigen 85B), a mycolyl transferase., Anderson DH, Harth G, Horwitz MA, Eisenberg D, J Mol Biol. 2001 Mar 23;307(2):671-81. PMID:11254389

Page seeded by OCA on Tue Nov 20 14:30:13 2007