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Catalytic Site Atlas Search Results
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Catalytic Site Atlas

CSA LITERATURE entry for 1vom

E.C. nameMYOSIN
SpeciesDictyostelium discoideum (Slime mould)
E.C. Number (IntEnz) -.-.-.-
CSA Homologues of 1vomThere are 83 Homologs
CSA Entries With UniProtID
CSA Entries With EC Number -.-.-.-
PDBe Entry 1vom
PDBSum Entry 1vom
MACiE Entry 1vom

Literature Report

IntroductionMyosin is the key enzyme in transducing the energy from ATP hydrolysis into directed movement. Muscle contraction involves the relative movements of myosin and actin filaments. This movement is achieved by the interaction of the globular heads of myosin with actin, and is driven by the hydrolysis of ATP in the myosin head domains.
MechansimBinding of ATP to the active site induces cleft closure with Glu 459 moving to form a salt bridge with Arg 238. The 'lytic' water molecule is released from Arg 238 and positioned for nucleophilic attack on the gamma phosphate by interactions with Ser 237 and with a second water molecule that interacts wih Glu 459 and the backbone oxygen of Gly 457. Departure of the gamma phosphate of ATP from the beta phosphate is promoted by a hydrogen bond from a gamma phosphate oxygen to the backbone NH group of Gly 457; this hydrogen bond forms specifically in the transition state. Attack by the lytic water molecule on the gamma phosphate is promoted by deprotonation of this water by the second water (which ends up as a hydronium ion, one of the reaction products as determined experimentally). Positive charge accumulation on this second water molecule is stabilised by its interactions with Glu 459 and with Gly 457. Accumulation of negative charge on the beta-gamma bridging oxygen as it departs from the gamma phosphate is stabilised by interactions of this atom to the side chain NH2 of Asn 233 and the backbone NH of Gly 182.

Catalytic Sites for 1vom

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA459459macie:sideChainProposed to stabilise accumulation of positive charge on the water molecule that deprotonates the lytic water.
GlyA182182macie:mainChainAmideBackbone amide stabilises accumulation of negative charge on the beta-gamma bridging oxygen as this atom departs from the gamma phosphate.
GlyA457457macie:mainChainAmideBackbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. Backbone O is proposed to interact with and stabilise accumulation of positive charge on the water molecule that deprotonates the lytic water.
GlyA457457macie:mainChainCarbonylBackbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. Backbone O is proposed to interact with and stabilise accumulation of positive charge on the water molecule that deprotonates the lytic water.
AsnA233233macie:sideChainSide chain amide stabilises accumulation of negative charge on the beta-gamma bridging oxygen as this atom departs from the gamma phosphate.

Literature References

Notes:Various mechanims that differ from that given here have been proposed, including the involvement of Ser 236 in proton transfer (ref 7619795). The recent proposal of Onishi et al (ref 15049682) has been used for this entry. In many enzymatic phosphoryl transfer reactions, positively charged ions around the gamma and beta phosphates of ATP have been implicated in stabilising negative charge in the transition state. In the myosin active site, Lys 185 and an Mg2+ ion are present; however the mutation K185A does not abolish catalysis (see ref 15049682). In addition, if the transition state for NTP hydrolysis is dissociative rather than associative in nature, placing positive charges around the gamma phosphate would not be catalytic (see for example Admiraal and Herschlag, Chem Biol. 1995 Nov;2(11):729-39.)
Onishi H
On the myosin catalysis of ATP hydrolysis.
Biochemistry 2004 43 3757-3763
PubMed: 15049682
Onishi H
Functional transitions in myosin: role of highly conserved Gly and Glu residues in the active site.
Biochemistry 1997 36 3767-3772
PubMed: 9092805
Onishi H
Early stages of energy transduction by myosin: roles of Arg in switch I, of Glu in switch II, and of the salt-bridge between them.
Proc Natl Acad Sci U S A 2002 99 15339-15344
PubMed: 12429851
Smith CA
X-ray structure of the magnesium(II).ADP.vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution.
Biochemistry 1996 35 5404-5417
PubMed: 8611530
Fisher AJ
X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-.
Biochemistry 1995 34 8960-8972
PubMed: 7619795
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