Darshan V Trivedi, Suman Nag, Annamma Spudich, Kathleen M Ruppel, James A Spudich
{"title":"肌球蛋白机械酶家族:从机制到治疗方法。","authors":"Darshan V Trivedi, Suman Nag, Annamma Spudich, Kathleen M Ruppel, James A Spudich","doi":"10.1146/annurev-biochem-011520-105234","DOIUrl":null,"url":null,"abstract":"<p><p>Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin family members are likely to be potentially unique targets for treating other diseases as well. The first part of this review focuses on how myosins convert the chemical energy of ATP hydrolysis into mechanical movement, followed by a description of existing therapeutic approaches to target human β-cardiac myosin. The next section focuses on the possibility of targeting nonmuscle members of the human myosin family for several diseases. We end the review by describing the roles of myosin in parasites and the therapeutic potential of targeting them to block parasitic invasion of their hosts.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"89 ","pages":"667-693"},"PeriodicalIF":12.1000,"publicationDate":"2020-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742983/pdf/nihms-1710843.pdf","citationCount":"0","resultStr":"{\"title\":\"The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.\",\"authors\":\"Darshan V Trivedi, Suman Nag, Annamma Spudich, Kathleen M Ruppel, James A Spudich\",\"doi\":\"10.1146/annurev-biochem-011520-105234\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin family members are likely to be potentially unique targets for treating other diseases as well. The first part of this review focuses on how myosins convert the chemical energy of ATP hydrolysis into mechanical movement, followed by a description of existing therapeutic approaches to target human β-cardiac myosin. The next section focuses on the possibility of targeting nonmuscle members of the human myosin family for several diseases. We end the review by describing the roles of myosin in parasites and the therapeutic potential of targeting them to block parasitic invasion of their hosts.</p>\",\"PeriodicalId\":7980,\"journal\":{\"name\":\"Annual review of biochemistry\",\"volume\":\"89 \",\"pages\":\"667-693\"},\"PeriodicalIF\":12.1000,\"publicationDate\":\"2020-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742983/pdf/nihms-1710843.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-biochem-011520-105234\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/3/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1146/annurev-biochem-011520-105234","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/3/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
肌球蛋白是生物学中最迷人的酶之一。肌球蛋白是一种极其异构的化学机械分子机器,参与了无数关键的细胞功能,而且经常是导致疾病表型的突变部位。人类β-心肌肌球蛋白已被证明是治疗心肌疾病的小分子疗法的绝佳靶点,正如我们在本文中所描述的,肌球蛋白家族的其他成员也可能是治疗其他疾病的潜在独特靶点。本综述的第一部分重点介绍肌球蛋白如何将 ATP 水解的化学能转化为机械运动,然后介绍针对人类 β-心肌肌球蛋白的现有治疗方法。下一节重点探讨了针对人类肌球蛋白家族非肌肉成员治疗多种疾病的可能性。最后,我们介绍了肌球蛋白在寄生虫中的作用,以及以肌球蛋白为靶点阻止寄生虫入侵宿主的治疗潜力。
The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.
Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin family members are likely to be potentially unique targets for treating other diseases as well. The first part of this review focuses on how myosins convert the chemical energy of ATP hydrolysis into mechanical movement, followed by a description of existing therapeutic approaches to target human β-cardiac myosin. The next section focuses on the possibility of targeting nonmuscle members of the human myosin family for several diseases. We end the review by describing the roles of myosin in parasites and the therapeutic potential of targeting them to block parasitic invasion of their hosts.
期刊介绍:
The Annual Review of Biochemistry, in publication since 1932, sets the standard for review articles in biological chemistry and molecular biology. Since its inception, these volumes have served as an indispensable resource for both the practicing biochemist and students of biochemistry.