scholarly journals Switch‐1 Instability at the Active Site Decouples ATP Hydrolysis from Force Generation in Myosin II

Cytoskeleton ◽  
2020 ◽  
Author(s):  
Benjamin C. Walker ◽  
Claire E. Walczak ◽  
Jared C. Cochran
Keyword(s):  
Active Site ◽  
Atp Hydrolysis ◽  
Myosin Ii ◽  
Force Generation

scholarly journals Switch-1 Instability at the Active Site Decouples ATP Hydrolysis from Force Generation in Myosin II

2020 ◽  
Author(s):  
Benjamin C. Walker ◽  
Claire E. Walczak ◽  
Jared C. Cochran
Keyword(s):  
Binding Site ◽  
Active Site ◽  
Atp Hydrolysis ◽  
Slight Modification ◽  
Divalent Metal ◽  
Force Generation ◽  
Single Atom ◽  
Actin Binding ◽  
Power Stroke ◽  
Tight Coupling

AbstractMyosin active site elements (i.e. switch-1) bind both ATP and a divalent metal to coordinate ATP hydrolysis. ATP hydrolysis at the active site is linked via allosteric communication to the actin polymer binding site and lever arm movement, thus coupling the free energy of ATP hydrolysis to force generation. How active site motifs are functionally linked to actin binding and the power stroke is still poorly understood. We hypothesize that destabilizing switch-1 movement at the active site will negatively affect the tight coupling of ATP hydrolysis to force production. Using a metal-switch system, we tested the effect of interfering with switch-1 coordination of the divalent metal cofactor on force generation. We found that while ATPase activity increased, motility was inhibited. Our results demonstrate that a single atom change that affects the switch-1 interaction with the divalent metal directly regulates actin binding and force generation. Even slight modification of the switch-1 divalent metal coordination can decouple ATP hydrolysis from motility. Switch-1 movement is therefore critical for both structural communication with the actin binding site, as well as coupling the energy of ATP hydrolysis to force generation.

scholarly journals Amino acid sequence of the active site of Acanthamoeba myosin II.

1986 ◽  
Vol 261 (4) ◽  
pp. 1844-1848
Author(s):  
M A Atkinson ◽  
E A Robinson ◽  
E Appella ◽  
E D Korn
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Active Site ◽  
Myosin Ii

scholarly journals Myosinome: A Database of Myosins from Select Eukaryotic Genomes to Facilitate Analysis of Sequence-Structure-Function Relationships

2012 ◽  
Vol 6 ◽  
pp. BBI.S9902 ◽  
Author(s):  
Divya P. Syamaladevi ◽  
Margaret S Sunitha ◽  
S. Kalaimathy ◽  
Chandrashekar C. Reddy ◽  
Mohammed Iftekhar ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Atp Hydrolysis ◽  
Homo Sapiens ◽  
Relevant Literature ◽  
Myosin Ii ◽  
Coiled Coil ◽  
Structural Features ◽  
Model Organisms ◽  
Congenital Diseases ◽  
C Elegans

Myosins are one of the largest protein superfamilies with 24 classes. They have conserved structural features and catalytic domains yet show huge variation at different domains resulting in a variety of functions. Myosins are molecules driving various kinds of cellular processes and motility until the level of organisms. These are ATPases that utilize the chemical energy released by ATP hydrolysis to bring about conformational changes leading to a motor function. Myosins are important as they are involved in almost all cellular activities ranging from cell division to transcriptional regulation. They are crucial due to their involvement in many congenital diseases symptomatized by muscular malfunctions, cardiac diseases, deafness, neural and immunological dysfunction, and so on, many of which lead to death at an early age. We present Myosinome, a database of selected myosin classes (myosin II, V, and VI) from five model organisms. This knowledge base provides the sequences, phylogenetic clustering, domain architectures of myosins and molecular models, structural analyses, and relevant literature of their coiled-coil domains. In the current version of Myosinome, information about 71 myosin sequences belonging to three myosin classes (myosin II, V, and VI) in five model organisms ( Homo Sapiens, Mus musculus, D. melanogaster, C. elegans and S. cereviseae) identified using bioinformatics surveys are presented, and several of them are yet to be functionally characterized. As these proteins are involved in congenital diseases, such a database would be useful in short-listing candidates for gene therapy and drug development. The database can be accessed from http://caps.ncbs.res.in/myosinome .

scholarly journals Mechanochemical Function of Myosin II: Investigation into the Recovery Stroke and ATP Hydrolysis

2020 ◽  
Vol 124 (45) ◽  
pp. 10014-10023
Author(s):  
Anthony P. Baldo ◽  
Jil C. Tardiff ◽  
Steven D. Schwartz
Keyword(s):  
Atp Hydrolysis ◽  
Myosin Ii ◽  
Recovery Stroke

scholarly journals Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophie L. Mader ◽  
Abraham Lopez ◽  
Jannis Lawatscheck ◽  
Qi Luo ◽  
Daniel A. Rutz ◽  
...  
Keyword(s):  
Molecular Chaperone ◽  
Active Site ◽  
Large Scale ◽  
Atp Hydrolysis ◽  
Mechanistic Model ◽  
Ion Pairs ◽  
Conformational Dynamics ◽  
Heat Shock Protein 90 ◽  
Eukaryotic Cell ◽  
Atpase Reaction

AbstractThe heat shock protein 90 (Hsp90) is a molecular chaperone that employs the free energy of ATP hydrolysis to control the folding and activation of several client proteins in the eukaryotic cell. To elucidate how the local ATPase reaction in the active site couples to the global conformational dynamics of Hsp90, we integrate here large-scale molecular simulations with biophysical experiments. We show that the conformational switching of conserved ion pairs between the N-terminal domain, harbouring the active site, and the middle domain strongly modulates the catalytic barrier of the ATP-hydrolysis reaction by electrostatic forces. Our combined findings provide a mechanistic model for the coupling between catalysis and protein dynamics in Hsp90, and show how long-range coupling effects can modulate enzymatic activity.

scholarly journals The reversibility of adenosine triphosphate cleavage by myosin

1973 ◽  
Vol 133 (2) ◽  
pp. 323-328 ◽  
Author(s):  
C. R. Bagshaw ◽  
D. R. Trentham
Keyword(s):  
Muscle Contraction ◽  
Active Site ◽  
Energy Exchange ◽  
Atp Hydrolysis ◽  
Mechanical Energy ◽  
Standard Free Energy ◽  
Standard Free Energy Change ◽  
Heavy Meromyosin ◽  
Cleavage Step ◽  
Hydrolysis Of

For the simplest kinetic model the reverse rate constants (k−1 and k−2) associated with ATP binding and cleavage on purified heavy meromyosin and heavy meromyosin subfragment 1 from rabbit skeletal muscle in the presence of 5mm-MgCl2, 50mm-KCl and 20mm-Tris–HCl buffer at pH8.0 and 22°C are: k−1<0.02s−1 and k−1=16s−1. Apparently, higher values of k−1 and k−2 are found with less-purified protein preparations. The values of k−1 and k−2 satisfy conditions required by previous 18O-incorporation studies of H218O into the Pi moiety on ATP hydrolysis and suggest that the cleavage step does involve hydrolysis of ATP or formation of an adduct between ATP and water. The equilibrium constant for the cleavage step at the myosin active site is 9. If the cycle of events during muscle contraction is described by the model proposed by Lymn & Taylor (1971), the fact that there is only a small negative standard free-energy change for the cleavage step is advantageous for efficient chemical to mechanical energy exchange during muscle contraction.

scholarly journals The interplay of DNA binding, ATP hydrolysis and helicase activities of the archaeal MCM helicase

2011 ◽  
Vol 436 (2) ◽  
pp. 409-414 ◽  
Author(s):  
Li Phing Liew ◽  
Stephen D. Bell
Keyword(s):  
Dna Binding ◽  
Active Site ◽  
Atp Hydrolysis ◽  
Sulfolobus Solfataricus ◽  
Active Form ◽  
Dna Helicase ◽  
Atpase Domain ◽  
Minichromosome Maintenance ◽  
Conserved Residues ◽  
Mcm Helicase

The MCM (minichromosome maintenance) proteins of archaea are widely believed to be the replicative DNA helicase of these organisms. Most archaea possess a single MCM orthologue that forms homo-multimeric assemblies with a single hexamer believed to be the active form. In the present study we characterize the roles of highly conserved residues in the ATPase domain of the MCM of the hyperthermophilic archaeon Sulfolobus solfataricus. Our results identify a potential conduit for communicating DNA-binding information to the ATPase active site.

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