The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.

Autor: Trivedi DV; Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA; email: darshandaasro@gmail.com, kathleen.ruppel@gmail.com, jaspudich@gmail.com.; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA., Nag S; MyoKardia Inc., Brisbane, California 94005, USA; email: sumannag@gmail.com., Spudich A; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560-097, India; email: aspudich@gmail.com., Ruppel KM; Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA; email: darshandaasro@gmail.com, kathleen.ruppel@gmail.com, jaspudich@gmail.com.; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA.; Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA., Spudich JA; Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA; email: darshandaasro@gmail.com, kathleen.ruppel@gmail.com, jaspudich@gmail.com.; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
Jazyk: angličtina
Zdroj: Annual review of biochemistry [Annu Rev Biochem] 2020 Jun 20; Vol. 89, pp. 667-693. Date of Electronic Publication: 2020 Mar 13.
DOI: 10.1146/annurev-biochem-011520-105234
Abstrakt: 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.
Databáze: MEDLINE