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PDBsum entry 3myh
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Structural protein
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PDB id
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3myh
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References listed in PDB file
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Key reference
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Title
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Insights into the importance of hydrogen bonding in the gamma-Phosphate binding pocket of myosin: structural and functional studies of serine 236.
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Authors
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J.J.Frye,
V.A.Klenchin,
C.R.Bagshaw,
I.Rayment.
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Ref.
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Biochemistry, 2010,
49,
4897-4907.
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PubMed id
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Abstract
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The active site of myosin contains a group of highly conserved amino acid
residues whose roles in nucleotide hydrolysis and energy transduction might
appear to be obvious from the initial structural and kinetic analyses but become
less clear on deeper investigation. One such residue is Ser236 (Dictyostelium
discoideum myosin II numbering) which was proposed to be involved in a hydrogen
transfer network during gamma-phosphate hydrolysis of ATP, which would imply a
critical function in ATP hydrolysis and motility. The S236A mutant protein shows
a comparatively small decrease in hydrolytic activity and motility, and thus
this residue does not appear to be essential. To understand better the
contribution of Ser236 to the function of myosin, structural and kinetic studies
have been performed on the S236A mutant protein. The structures of the D.
discoideum motor domain (S1dC) S236A mutant protein in complex with magnesium
pyrophosphate, MgAMPPNP, and MgADP.vanadate have been determined. In contrast to
the previous structure of wild-type S1dC, the S236A.MgAMPPNP complex
crystallized in the closed state. Furthermore, transient-state kinetics showed a
4-fold reduction of the nucleotide release step, suggesting that the mutation
stabilizes a closed active site. The structures show that a water molecule
approximately adopts the location of the missing hydroxyl of Ser236 in the
magnesium pyrophosphate and MgAMPPNP structures. This study suggests that the
S236A mutant myosin proceeds via a different structural mechanism than wild-type
myosin, where the alternate mechanism is able to maintain near normal
transient-state kinetic values.
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