Polacek Norbert, Mankin Alexander S
Innsbruck Biocenter, Division of Genomics and RNomics, Innsbruck Medical University, Innsbruck, Austria.
Crit Rev Biochem Mol Biol. 2005 Sep-Oct;40(5):285-311. doi: 10.1080/10409230500326334.
The ribosomal peptidyl transferase center (PTC) resides in the large ribosomal subunit and catalyzes the two principal chemical reactions of protein synthesis: peptide bond formation and peptide release. The catalytic mechanisms employed and their inhibition by antibiotics have been in the focus of molecular and structural biologists for decades. With the elucidation of atomic structures of the large ribosomal subunit at the dawn of the new millennium, these questions gained a new level of molecular significance. The crystallographic structures compellingly confirmed that peptidyl transferase is an RNA enzyme. This places the ribosome on the list of naturally occurring ribozymes that outlived the transition from the pre-biotic RNA World to contemporary biology. Biochemical, genetic and structural evidence highlight the role of the ribosome as an entropic catalyst that accelerates peptide bond formation primarily by substrate positioning. At the same time, peptide release should more strongly depend on chemical catalysis likely involving an rRNA group of the PTC. The PTC is characterized by the most pronounced accumulation of universally conserved rRNA nucleotides in the entire ribosome. Thus, it came as a surprise that recent findings revealed an unexpected high level of variation in the mode of antibiotic binding to the PTC of ribosomes from different organisms.
核糖体肽基转移酶中心（PTC）位于核糖体大亚基中，催化蛋白质合成的两个主要化学反应：肽键形成和肽释放。几十年来，所采用的催化机制及其被抗生素抑制的情况一直是分子和结构生物学家关注的焦点。随着新千年伊始核糖体大亚基原子结构的阐明，这些问题在分子层面上有了新的意义。晶体学结构有力地证实了肽基转移酶是一种RNA酶。这使核糖体跻身于自然存在的核酶之列，这些核酶在从前生物RNA世界向当代生物学的转变中留存了下来。生化、遗传和结构证据突出了核糖体作为一种熵催化剂的作用，它主要通过底物定位来加速肽键形成。与此同时，肽释放可能更强烈地依赖于化学催化，这可能涉及PTC的一个rRNA基团。PTC的特征是在整个核糖体中普遍保守的rRNA核苷酸积累最为显著。因此，最近的研究结果表明，不同生物体核糖体的抗生素与PTC结合模式存在意想不到的高度差异，这令人惊讶。
