title: Mechanism of chiral proofreading during translation of the genetic code.
abstract: The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. The crystal structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with a substrate-mimicking analog shows how it uses an invariant 'cross-subunit' Gly-cisPro dipeptide to capture the chiral centre of incoming D-aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the unique side chain-independent mode of substrate recognition provides a clear explanation for DTD's ability to act on multiple D-amino acids. The strict chiral specificity elegantly explains how the enriched cellular pool of L-aminoacyl-tRNAs escapes this proofreading step. The study thus provides insights into a fundamental enantioselection process and elucidates a chiral enforcement mechanism with a crucial role in preventing D-amino acid infiltration during the evolution of translational apparatus. DOI: http://dx.doi.org/10.7554/eLife.01519.001.
authors.affiliation: Structural Biology Laboratory, Centre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Hyderabad, India.
authors.forename: Sadeem
authors.initials: S
authors.lastname: Ahmad
authors.forename: Satya Brata
authors.initials: SB
authors.lastname: Routh
authors.forename: Venu
authors.initials: V
authors.lastname: Kamarthapu
authors.forename: Jisha
authors.initials: J
authors.lastname: Chalissery
authors.forename: Sowndarya
authors.initials: S
authors.lastname: Muthukumar
authors.forename: Tanweer
authors.initials: T
authors.lastname: Hussain
authors.forename: Shobha P
authors.initials: SP
authors.lastname: Kruparani
authors.forename: Mandar V
authors.initials: MV
authors.lastname: Deshmukh
authors.forename: Rajan
authors.initials: R
authors.lastname: Sankaranarayanan
mesh_terms: D000241:Adenosine / Q000378:metabolism; D020134:Catalytic Domain; D003460:Crystallization; D019281:Dimerization; D005815:Genetic Code; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000241:Adenosine
keywords: enzyme mechanism; homochirality; proofreading; translation