The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches

Annu Rev Biochem. 2020 Jun 20;89:667-693. doi: 10.1146/annurev-biochem-011520-105234. Epub 2020 Mar 13.

Abstract

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.

Keywords: cancer; interacting heads motif; myosin; parasites; therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation / drug effects
  • Animals
  • Biomechanical Phenomena
  • Cryptosporidium / drug effects
  • Cryptosporidium / enzymology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use*
  • Gene Expression
  • Heart Failure / drug therapy*
  • Heart Failure / enzymology
  • Heart Failure / genetics
  • Heart Failure / pathology
  • Humans
  • Multigene Family
  • Mutation
  • Myosins / antagonists & inhibitors
  • Myosins / classification
  • Myosins / genetics
  • Myosins / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / enzymology
  • Nervous System Diseases / genetics
  • Nervous System Diseases / pathology
  • Plasmodium / drug effects
  • Plasmodium / enzymology
  • Protozoan Infections / drug therapy*
  • Protozoan Infections / enzymology
  • Protozoan Infections / genetics
  • Protozoan Infections / pathology
  • Toxoplasma / drug effects
  • Toxoplasma / enzymology

Substances

  • Enzyme Inhibitors
  • Adenosine Triphosphate
  • Myosins