PDBsum entry 1r88

Immune system

PDB id: 1r88

Contents

Protein chains

267 a.a. *

Waters ×400

* Residue conservation analysis

PDB id:

1r88

Name:

Immune system

Title:

The crystal structure of mycobacterium tuberculosis mpt51 (fbpc1)

Structure:

Mpt51/mpb51 antigen. Chain: a, b. Synonym: fibronectin-binding protein c1 (fbpc1, mpt51). Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: fbpc1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.71Å R-factor: 0.190 R-free: 0.205

Authors:

R.A.Wilson,W.N.Maughan,L.Kremer,G.S.Besra,K.Futterer

Key ref:

R.A.Wilson et al. (2004). The structure of Mycobacterium tuberculosis MPT51 (FbpC1) defines a new family of non-catalytic alpha/beta hydrolases. J Mol Biol, 335, 519-530. PubMed id: 14672660 DOI: 10.1016/j.jmb.2003.11.001

Date:

23-Oct-03 Release date: 30-Dec-03

Protein chains

P9WQN7  (MPT51_MYCTU) -  MPT51/MPB51 antigen from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 299 a.a.

Struc: 267 a.a.

DOI no: 10.1016/j.jmb.2003.11.001

J Mol Biol 335:519-530 (2004)

PubMed id: 14672660

The structure of Mycobacterium tuberculosis MPT51 (FbpC1) defines a new family of non-catalytic alpha/beta hydrolases.

R.A.Wilson, W.N.Maughan, L.Kremer, G.S.Besra, K.Fütterer.

ABSTRACT

Mycobacterium tuberculosis, the causative agent of tuberculosis, is known to secrete a number of highly immunogenic proteins that are thought to confer pathogenicity, in part, by mediating binding to host tissues. Among these secreted proteins are the trimeric antigen 85 (Ag85) complex and the related MPT51 protein, also known as FbpC1. While the physiological function of Ag85, a mycolyltransferase required for the biosynthesis of the cell wall component alpha,alpha'-trehalose dimycolate (or cord factor), has been identified recently, the function of the closely related MPT51 (approximately 40% identity with the Ag85 components) remains to be established. The crystal structure of M.tuberculosis MPT51, determined to 1.7 A resolution, shows that MPT51, like the Ag85 components Ag85B and Ag85C2, folds as an alpha/beta hydrolase, but it does not contain any of the catalytic elements required for mycolyltransferase activity. Moreover, the absence of a recognizable alpha,alpha'-trehalose monomycolate-binding site and the failure to detect an active site suggest that the function of MPT51 is of a non-enzymatic nature and that MPT51 may in fact represent a new family of non-catalytic alpha/beta hydrolases. Previous experimental evidence and the structural similarity to some integrins and carbohydrate-binding proteins led to the hypothesis that MPT51 might have a role in host tissue attachment, whereby ligands may include the serum protein fibronectin and small sugars.

Selected figure(s)

Figure 2.
Figure 2. Stereo views of the tertiary structure of MPT51, the structural superimposition with Ag85C2 and of the "active site". (a) Secondary structure is color-coded: green, b-sheet; cyan, a-helix; dark blue, 3[10] helix. The residues corresponding to the catalytic triad in the Ag85 subunits are shown as rods (yellow, carbon; blue, nitrogen; red, oxygen). (b) Illustration of structural differences between MPT51 and Ag85C2. Ribbon in light and dark blue corresponds to the active and inhibitor-bound forms of Ag85C2. The b7-a9 loop and helix a9 of MPT51 is shown in red, the fibronectin-binding loop in green. (c) Electron density (s[A]-weighted 2F[o] -F[c] map, 30-1.7 Å, after automatic backbone tracing in ARP/wARP, contour level 1.2s) of the active site of MPT51 with the catalytic triad of Ag85C2 superimposed (rods in light blue). The final refined model of MPT51 is shown with rods color-coded as in (a). The Figure was prepared using RIBBONS.[53.]

Figure 3.
Figure 3. (a) Stereo view of cavities in Ag85C2 (gray) versus MPT51 (cyan) superimposed with the ribbon diagram of MPT51. The trehalose molecule of the structure of Ag85B[20.] is shown as a guide for the eye. (b) Stereo view of the superimposition of the structures of the effector domain of E. coli TreR[37.] (blue) and of the S. typhimurium glucose/galactose receptor[38.] (green) with MPT51 (gray). The trehalose-6-phosphate ligand of TreR (red rods) and the trehalose molecule (yellow) of the Ag85B structure are shown. (c) and (d) Surface diagrams of (c) MPT51 and (d) Ag85B colored according to sequence conservation (red=identity). The surface area corresponding to the fibronectin-binding loop is marked in green. The Figure was prepared using (a) SURFNET, [28.] (a) and (b) RIBBONS [53.] and (c) GRASP. [54.]

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 335, 519-530) copyright 2004.

Figures were selected by an automated process.