Lu Kun Ping, Finn Greg, Lee Tae Ho, Nicholson Linda K
Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 1030, Boston, Massachusetts 02215, USA.
Nat Chem Biol. 2007 Oct;3(10):619-29. doi: 10.1038/nchembio.2007.35.
Proline is unique in the realm of amino acids in its ability to adopt completely distinct cis and trans conformations, which allows it to act as a backbone switch that is controlled by prolyl cis-trans isomerization. This intrinsically slow interconversion can be catalyzed by the evolutionarily conserved group of peptidyl prolyl cis-trans isomerase enzymes. These enzymes include cyclophilins and FK506-binding proteins, which are well known for their isomerization-independent role as cellular targets for immunosuppressive drugs. The significance of enzyme-catalyzed prolyl cis-trans isomerization as an important regulatory mechanism in human physiology and pathology was not recognized until the discovery of the phosphorylation-specific prolyl isomerase Pin1. Recent studies indicate that both phosphorylation-dependent and phosphorylation-independent prolyl cis-trans isomerization can act as a novel molecular timer to help control the amplitude and duration of a cellular process, and prolyl cis-trans isomerization might be a new target for therapeutic interventions.
脯氨酸在氨基酸领域独具特色，它能够呈现出完全不同的顺式和反式构象，这使其能够作为一种由脯氨酰顺反异构化控制的主链开关发挥作用。这种本质上缓慢的相互转化可由进化上保守的肽基脯氨酰顺反异构酶催化。这些酶包括亲环素和FK506结合蛋白，它们作为免疫抑制药物的细胞靶点，以其与异构化无关的作用而闻名。直到发现磷酸化特异性脯氨酰异构酶Pin1，酶催化的脯氨酰顺反异构化作为人类生理和病理中一种重要调节机制的意义才被认识到。最近的研究表明，磷酸化依赖性和磷酸化非依赖性的脯氨酰顺反异构化都可以作为一种新型分子定时器，帮助控制细胞过程的幅度和持续时间，并且脯氨酰顺反异构化可能是治疗干预的新靶点。
