Ahmad Sadeem, Routh Satya Brata, Kamarthapu Venu, Chalissery Jisha, Muthukumar Sowndarya, Hussain Tanweer, Kruparani Shobha P, Deshmukh Mandar V, Sankaranarayanan Rajan
Structural Biology Laboratory, Centre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Hyderabad, India.
Elife. 2013 Dec 3;2:e01519. doi: 10.7554/eLife.01519.
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.
生物大分子世界是同手性的,而这种同手性的有效维持和延续对于细胞存活至关重要。在本研究中,我们展示了一种构型特异性酶的作用机制,该酶能选择性地去除错误偶联到tRNA上的D-氨基酸。恶性疟原虫二聚体D-氨酰-tRNA脱酰基酶(DTD)与一种底物模拟类似物复合物的晶体结构表明,它是如何利用一个不变的“跨亚基”甘氨酸-顺式脯氨酸二肽来捕获进入的D-氨酰-tRNA的手性中心的。虽然没有蛋白质残基直接参与催化,但独特的不依赖于侧链的底物识别模式为DTD作用于多种D-氨基酸的能力提供了清晰的解释。严格的手性特异性巧妙地解释了L-氨酰-tRNA丰富的细胞池如何逃过这一校对步骤。因此,该研究为一个基本的对映体选择过程提供了见解,并阐明了一种在手性维持机制中起关键作用的机制,该机制在翻译装置进化过程中防止D-氨基酸渗入。DOI: http://dx.doi.org/10.7554/eLife.01519.001