title: A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography.
abstract: Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the L- and D-enantiomeric forms of Rv1738 enabled facile crystallization of the D/L-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing L- and D-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis.
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand; and.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bunker
authors.affiliation: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637.
authors.forename: Kalyaneswar
authors.initials: K
authors.lastname: Mandal
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand; and.
authors.forename: Ghader
authors.initials: G
authors.lastname: Bashiri
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand; and.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Chaston
authors.affiliation: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Pentelute
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand; and.
authors.forename: J Shaun
authors.initials: JS
authors.lastname: Lott
authors.affiliation: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637 ted.baker@auckland.ac.nz skent@uchicago.edu.
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery and School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand; and ted.baker@auckland.ac.nz skent@uchicago.edu.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry; D013237:Stereoisomerism; D013824:Thermus / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D011994:Recombinant Proteins
keywords: Mycobacterium tuberculosis; dormancy; protein structure; racemic protein crystallography; ribosome binding
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