The TB Structural Genomics Consortium: A decade of progress - 20/08/11

Doi : 10.1016/j.tube.2010.11.009

Nicholas Chim ^a, Jeff E. Habel ^c, Jodie M. Johnston ^d, Inna Krieger ^e, Linda Miallau ^f, Ramasamy Sankaranarayanan ^g, Robert P. Morse ^a, John Bruning ^e, Stephanie Swanson ^e, Haelee Kim ^e, Chang-Yub Kim ^h, Hongye Li ⁱ, Esther M. Bulloch ^d, Richard J. Payne ^j, Alexandra Manos-Turvey ^j, Li-Wei Hung ^c,^h, Edward N. Baker ^d, J. Shaun Lott ^d, Michael N.G. James ^g, Thomas C. Terwilliger ^h, David S. Eisenberg ^f, James C. Sacchettini ^e, Celia W. Goulding ^a,^b,^⁎
^a Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA
^b Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA
^c Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
^d School of Biological Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1142, New Zealand
^e Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA
^f UCLA-DOE Lab of Structural Biology, Howard Hughes Medical Institute, Molecular Biology Institute, University of California, UCLA Box 951570, Los Angeles, CA 90095, USA
^g Group in Protein Structure and Function, Department of Biochemistry, School of Molecular and Systems Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G2H7
^h Los Alamos National Laboratory, Los Alamos, NM 87545, USA
ⁱ Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA
^j School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia

Corresponding author. Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA. Tel.: +1 949 824 0037; fax: +1 949 824 8551.

Summary

The TB Structural Genomics Consortium is a worldwide organization of collaborators whose mission is the comprehensive structural determination and analyses of Mycobacterium tuberculosis proteins to ultimately aid in tuberculosis diagnosis and treatment. Congruent to the overall vision, Consortium members have additionally established an integrated facilities core to streamline M. tuberculosis structural biology and developed bioinformatics resources for data mining. This review aims to share the latest Consortium developments with the TB community, including recent structures of proteins that play significant roles within M. tuberculosis. Atomic resolution details may unravel mechanistic insights and reveal unique and novel protein features, as well as important protein–protein and protein–ligand interactions, which ultimately lead to a better understanding of M. tuberculosis biology and may be exploited for rational, structure-based therapeutics design.

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Keywords : Mycobacterium tuberculosis, Protein structure, X-ray crystallography, Structural genomics, Drug discovery

Abbreviations : Mtb, TB, TBSGC, Rv number, PDB, SAXS, PPI, ORF, NMR, ADC, PABA, OAT, OTC, ORN, NVA, CP, TCA, ICL, CoA, MSA, MSG, ATP, NAD, PEPCK, MhuD, Isd, Dsb, TA, SAD, SeMet

Plan

Introduction

The TBSGC structure determination pipeline (Li-Wei Hung, Chang-Yub Kim, Hongye Li, James C. Sacchettini and Thomas C. Terwilliger)

Solution and crystal structures of Mtb UreA - the implications in bio-molecular assembly and drug discovery of Mtb urease (Jeff E. Habel and Li-Wei Hung)

Studies on chorismate-utilizing enzymes in Mtb (Jodie M. Johnston, Esther M. Bulloch, Richard J. Payne, Alexandra Manos-Turvey, Edward N. Baker and J. Shaun Lott)

Design of compounds to inhibit salicylate synthase

Identification and characterization of 4-amino-4-deoxychorismate lyase

Ornithine acetyltransferase (Rv1653) and ornithine carbamoyltransferase (Rv1656) in arginine the biosynthesis pathway of Mtb (Ramasamy Sankaranarayanan and Michael N.G. James)

Structure of Ornithine Acetyltransferase (OAT) from Mtb

Structure of Ornithine Carbamoyltransferase (OTC) from Mtb

Structure of key enzymes in persistence related metabolic shift (Inna Krieger, John Bruning, Stephanie Swanson, Haelee Kim and James C. Sacchettini)

Structural and biochemical characterization of MhuD (Rv3592) and DsbF (Rv1677) (Nicholas Chim, Robert P. Morse and Celia W. Goulding)

Iron availability

Mtb disulfide oxidoreductase system: Mtb DsbF (Rv1677) and Mtb DsbE (Rv2878c)

Toxin–Antitoxin complexes from Mtb (Linda Miallau and David Eisenberg)

VapBC TA systems

RelBE TA systems

Conclusions

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Vol 91 - N° 2

P. 155-172 - mars 2011 Retour au numéro

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The TB Structural Genomics Consortium: A decade of progress - 20/08/11

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