Myosin ATPase

 

Myosin 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.

 

Reference Protein and Structure

Sequence
P08799 UniProt IPR027417 (Sequence Homologues) (PDB Homologues)
Biological species
Dictyostelium discoideum (Slime mould) Uniprot
PDB
1vom - COMPLEX BETWEEN DICTYOSTELIUM MYOSIN AND MGADP AND VANADATE AT 1.9A RESOLUTION (1.9 Å) PDBe PDBsum 1vom
Catalytic CATH Domains
3.40.850.10 CATHdb 1.20.58.530 CATHdb (see all for 1vom)
Cofactors
Magnesium(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:5.6.1.8)

ATP(4-)
CHEBI:30616ChEBI
+
water
CHEBI:15377ChEBI
→
ADP(3-)
CHEBI:456216ChEBI
+
hydron
CHEBI:15378ChEBI
+
hydrogenphosphate
CHEBI:43474ChEBI

Enzyme Mechanism

Introduction

Binding 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 Residues Roles

UniProt PDB* (1vom)
Asn233 Asn233A Side chain amide stabilises accumulation of negative charge on the beta-gamma bridging oxygen as this atom departs from the gamma phosphate. electrostatic stabiliser
Gly182 (main-N) Gly182A (main-N) Backbone amide stabilises accumulation of negative charge on the beta-gamma bridging oxygen as this atom departs from the gamma phosphate. electrostatic stabiliser
Gly457 (main-N) Gly457A (main-N) Backbone 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. electrostatic stabiliser
Glu459 Glu459A Proposed to stabilise accumulation of positive charge on the water molecule that deprotonates the lytic water. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Onishi H et al. (2004), Biochemistry, 43, 3757-3763. On the Myosin Catalysis of ATP Hydrolysis†. DOI:10.1021/bi040002m. PMID:15049682.
  2. Onishi H et al. (2002), Proc Natl Acad Sci U S A, 99, 15339-15344. Nonlinear partial differential equations and applications: 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. DOI:10.1073/pnas.242604099. PMID:12429851.
  3. Onishi H et al. (1997), Biochemistry, 36, 3767-3772. Functional Transitions in Myosin:  Role of Highly Conserved Gly and Glu Residues in the Active Site†. DOI:10.1021/bi9630772. PMID:9092805.
  4. Smith CA et al. (1996), Biochemistry, 35, 5404-5417. X-ray structure of the magnesium(II).ADP.vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution. DOI:10.1021/bi952633+. PMID:8611530.
  5. Fisher AJ et al. (1995), Biochemistry, 34, 8960-8972. X-ray Structures of the Myosin Motor Domain of Dictyostelium discoideum Complexed with MgADP.cntdot.BeFx and MgADP.cntdot.AlF4-. DOI:10.1021/bi00028a004. PMID:7619795.

Step 1.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Glu459A electrostatic stabiliser
Gly182A (main-N) electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser

Chemical Components

Step 1.

Introduction

A salt bridge is formed between Glu 459 and Arg 238 due to the binding of ATP to the active site which induces cleft closure with Glu 459. The 'lytic' water molecule is released from Arg 238 and positioned for nucleophilic attack on the gamma phosphate by interactions with Ser 237. For this mechanism water directly attacks the gamma phosphate of ATP. As ATP will deprotonate the water molecule itself to activate it so it can nucleophilically attack the phosphoryl. The negative charge that accumulates on the leaving group is stabilised by coordination to Mg2+ and hydrogen bonding to backbone amides of Gly182 and the side chain amide of Asn233.

Catalytic Residues Roles

UniProt PDB* (1vom)
Ser237, Thr186 Ser237A, Thr186A Forms Mg2+ binding site metal ligand
Asn233, Gly182 (main-N) Asn233A, Gly182A (main-N) Stabilises the negative charge that accumulates on the leaving group by hydrogen bonding from their respective amide groups. electrostatic stabiliser
Gly457 (main-N) Gly457A (main-N) Backbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

proton transfer, bimolecular nucleophilic addition, intermediate formation, overall reactant used, unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed

References

  1. Kiani FA et al. (2015), Curr Opin Struct Biol, 31, 115-123. Advances in quantum simulations of ATPase catalysis in the myosin motor. DOI:10.1016/j.sbi.2015.04.006. PMID:26005996.
  2. Grigorenko BL et al. (2011), J Mol Graph Model, 31, 1-4. Minimum energy reaction profiles for ATP hydrolysis in myosin. DOI:10.1016/j.jmgm.2011.07.005. PMID:21839658.
  3. Schwarzl SM et al. (2006), Biochemistry, 45, 5830-5847. Insights into the chemomechanical coupling of the myosin motor from simulation of its ATP hydrolysis mechanism. DOI:10.1021/bi052433q. PMID:16669626.
  4. Li G et al. (2004), J Phys Chem B, 108, 3342-3357. Mechanochemical Coupling in Myosin:  A Theoretical Analysis with Molecular Dynamics and Combined QM/MM Reaction Path Calculations. DOI:10.1021/jp0371783.
  5. Onishi H et al. (2004), Biochemistry, 43, 3757-3763. On the Myosin Catalysis of ATP Hydrolysis†. DOI:10.1021/bi040002m. PMID:15049682.
  6. Okimoto N et al. (2001), Biophys J, 81, 2786-2794. Theoretical Studies of the ATP Hydrolysis Mechanism of Myosin. DOI:10.1016/S0006-3495(01)75921-8.
  7. Bauer CB et al. (2000), J Biol Chem, 275, 38494-38499. X-ray structures of the apo and MgATP-bound states of Dictyostelium discoideum myosin motor domain. DOI:10.1074/jbc.M005585200. PMID:10954715.

Step 1. The gamma phosphate directly deprotonates a water which activates it to attack the phopshate.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly182A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand

Chemical Components

proton transfer, ingold: bimolecular nucleophilic addition, intermediate formation, overall reactant used

Step 2. The pentacoordinate transition state collapse resulting in the cleavage of the phopshodiester bond.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly182A (main-N) electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand
Asn233A electrostatic stabiliser

Chemical Components

ingold: unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed
Download: Image, Marvin File

Step 1. The gamma phosphate directly deprotonates a water which activates it to attack the phopshate.

Step 2. The pentacoordinate transition state collapse resulting in the cleavage of the phopshodiester bond.

Products.

Introduction

Binding 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 with Glu 459 and the backbone oxygen of Gly 457. The second water molecule protonates the gamma phosphate which then enables it to accept a proton from the "lytic water" which activates that water to nucleophilically attack the gamma phosphate. Which will produce the transition state which has a pentavalent gamma-phosphate in a bipyramidal configuration. The transition state collapses, cleaving the phosphodiester bond and the negative charge that accumulate on the leaving group is stabilised by the amide group of Gly 182 and Asn 233 and also by coordination to Mg2+ ion.

Catalytic Residues Roles

UniProt PDB* (1vom)
Ser237, Thr186 Ser237A, Thr186A Form Mg2+ binding site metal ligand
Asn233, Gly182 (main-N) Asn233A, Gly182A (main-N) Stabilises the accumulated negative charge on the leaving group electrostatic stabiliser
Gly457 (main-N) Gly457A (main-N) Backbone 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. electrostatic stabiliser
Glu459 Glu459A Stabilises and positions the water that deprotonates the lytic water
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

overall reactant used, intermediate formation, bimolecular nucleophilic addition, proton transfer, unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed

References

  1. Kiani FA et al. (2015), Curr Opin Struct Biol, 31, 115-123. Advances in quantum simulations of ATPase catalysis in the myosin motor. DOI:10.1016/j.sbi.2015.04.006. PMID:26005996.
  2. Kiani FA et al. (2014), Proc Natl Acad Sci U S A, 111, E2947-E2956. Catalytic strategy used by the myosin motor to hydrolyze ATP. DOI:10.1073/pnas.1401862111. PMID:25006262.
  3. Onishi H et al. (2004), Biochemistry, 43, 3757-3763. On the Myosin Catalysis of ATP Hydrolysis†. DOI:10.1021/bi040002m. PMID:15049682.

Step 1. The gamma phosphate directly deprotonates a water which activates it to deprotonate another water which can then nucleophilically attack the gamma phosphate

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly457A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly182A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand

Chemical Components

overall reactant used, intermediate formation, ingold: bimolecular nucleophilic addition, proton transfer

Step 2. The pentavalent transition state collapses resulting in the cleavage of the phosphodiester bond.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly182A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand

Chemical Components

ingold: unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed
Download: Image, Marvin File

Step 1. The gamma phosphate directly deprotonates a water which activates it to deprotonate another water which can then nucleophilically attack the gamma phosphate

Step 2. The pentavalent transition state collapses resulting in the cleavage of the phosphodiester bond.

Products.

Introduction

The lytic water, which is released due to the formation of a salt bridge between Glu 459 and Arg 238 when ATP binds, can nucleophilically attack the gamma phosphate after it is deprotonated by Ser 236 which is deprotonated by the gamma phosphate. The pentavalent transition state formed will then collapse resulting in the cleavage of the phosphodiester bond. The negative charge that then accumulates on the leaving group is stabilised by the backbone and side chain amide groups on Gly 182 and Asn 233 and also the Mg2+ ion.

Catalytic Residues Roles

UniProt PDB* (1vom)
Ser236 Ser236A Acts as a general acid/base as is deprotonated by the gamma phosphate of ATP to enable it to accept a proton from a water which activates the water for nucleophilic attack. proton relay, proton acceptor, proton donor
Ser237, Thr186 Ser237A, Thr186A Forms Mg2+ binding site metal ligand
Asn233, Gly182 (main-N) Asn233A, Gly182A (main-N) Stabilises the accumulated negative charge on the leaving group electrostatic stabiliser
Gly457 (main-N) Gly457A (main-N) Backbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

overall reactant used, intermediate formation, bimolecular nucleophilic addition, proton transfer, unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed

References

  1. Kiani FA et al. (2015), Curr Opin Struct Biol, 31, 115-123. Advances in quantum simulations of ATPase catalysis in the myosin motor. DOI:10.1016/j.sbi.2015.04.006. PMID:26005996.
  2. Yang Y et al. (2008), J Mol Biol, 381, 1407-1420. Extensive conformational transitions are required to turn on ATP hydrolysis in myosin. DOI:10.1016/j.jmb.2008.06.071. PMID:18619975.
  3. Schwarzl SM et al. (2006), Biochemistry, 45, 5830-5847. Insights into the chemomechanical coupling of the myosin motor from simulation of its ATP hydrolysis mechanism. DOI:10.1021/bi052433q. PMID:16669626.
  4. Li G et al. (2004), J Phys Chem B, 108, 3342-3357. Mechanochemical Coupling in Myosin:  A Theoretical Analysis with Molecular Dynamics and Combined QM/MM Reaction Path Calculations. DOI:10.1021/jp0371783.
  5. Onishi H et al. (2004), Biochemistry, 43, 3757-3763. On the Myosin Catalysis of ATP Hydrolysis†. DOI:10.1021/bi040002m. PMID:15049682.

Step 1. The gamma phosphate deprotonates Ser236 which enables it to accept a proton from the lytic water which can now nucleophilically attack the the gamma phosphate.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly457A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly182A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand
Ser236A proton acceptor, proton donor, proton relay

Chemical Components

overall reactant used, intermediate formation, ingold: bimolecular nucleophilic addition, proton transfer

Step 2. The pentavalent transition state collapses resulting in the cleavage of the phosphodiester bond.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly182A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand

Chemical Components

ingold: unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed
Download: Image, Marvin File

Step 1. The gamma phosphate deprotonates Ser236 which enables it to accept a proton from the lytic water which can now nucleophilically attack the the gamma phosphate.

Step 2. The pentavalent transition state collapses resulting in the cleavage of the phosphodiester bond.

Products.

Introduction

As ATP binds and induces cleft closure so that the lytic water can be released from Arg 238 as it forms a salt bridge with Glu 459; Ser 181 is deprotonated by the gamma phosphate. This enables it to accept a proton from the lytic water so that the water can then nucleophilically attack the gamma phosphate. The transition state will collapse resulting in the cleavage of the phosphodiester bond and the leaving group, beta-phosphate will be stabilised by the backbone amide of Gly 182 and the sidechain amide of Asn 233, as well as the magnesium ion.

Catalytic Residues Roles

UniProt PDB* (1vom)
Ser181 Ser181A Acts as a general acid/ base as is deprotonated by the gamma phosphate which enables it to activate the lytic water by deprotonating it so that the water can act as a nucleophile. proton relay, proton acceptor, proton donor
Ser237, Thr186 Ser237A, Thr186A Forms the Mg2+ binding site metal ligand
Asn233, Gly182 (main-N) Asn233A, Gly182A (main-N) Stabilises the accumulate negative charge on the leaving group, beta phosphate. electrostatic stabiliser
Gly457 (main-N) Gly457A (main-N) Backbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

overall reactant used, intermediate formation, bimolecular nucleophilic addition, proton transfer, unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed

References

  1. Kiani FA et al. (2015), Curr Opin Struct Biol, 31, 115-123. Advances in quantum simulations of ATPase catalysis in the myosin motor. DOI:10.1016/j.sbi.2015.04.006. PMID:26005996.
  2. Grigorenko BL et al. (2011), J Mol Graph Model, 31, 1-4. Minimum energy reaction profiles for ATP hydrolysis in myosin. DOI:10.1016/j.jmgm.2011.07.005. PMID:21839658.
  3. Schwarzl SM et al. (2006), Biochemistry, 45, 5830-5847. Insights into the chemomechanical coupling of the myosin motor from simulation of its ATP hydrolysis mechanism. DOI:10.1021/bi052433q. PMID:16669626.
  4. Onishi H et al. (2004), Biochemistry, 43, 3757-3763. On the Myosin Catalysis of ATP Hydrolysis†. DOI:10.1021/bi040002m. PMID:15049682.

Step 1. Ser181 is deprotonated by the gamma phosphate which enables it to accept a proton from the lytic water. This activates the water to nucleophilically attack the gamma phosphate.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly457A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly182A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand
Ser181A proton acceptor, proton donor, proton relay

Chemical Components

overall reactant used, intermediate formation, ingold: bimolecular nucleophilic addition, proton transfer

Step 2. The pentavalent transition state collapses resulting in the cleavage of the phosphodiester bond.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly182A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand

Chemical Components

ingold: unimolecular elimination by the conjugate base, inferred reaction step, intermediate collapse, overall product formed
Download: Image, Marvin File

Step 1. Ser181 is deprotonated by the gamma phosphate which enables it to accept a proton from the lytic water. This activates the water to nucleophilically attack the gamma phosphate.

Step 2. The pentavalent transition state collapses resulting in the cleavage of the phosphodiester bond.

Products.

Introduction

Glu 459 can accept a proton from a water which enables it to accept a proton from the lytic water which activates that water to nucleophilially attack the gamma phosphate to produce the pentavalent transition state. Ser 181 then is deprotonated by the gamma phosphate which then enables it to accept a proton from a thrid water which will then accept a proton from Glu 459 and thus returning Glu 459 to its original protonation state. The protonation of the gamma phosphate also induces an elimination and as a result the phosphodiester bond is cleaved. The beta phosphate leaving group accumulates a negative charge which is stabilised by the backbone amide of Gly 182 and the side chain amide of Asn 233 as well as the magnesium ion.

Catalytic Residues Roles

UniProt PDB* (1vom)
Ser181 Ser181A protonates the gamma phosphate so that it can accept a proton from a water which enables said water to regenerate the original protonation state of Glu 459. proton relay, proton acceptor, proton donor
Ser237, Thr186 Ser237A, Thr186A Forms Mg2+ binding site metal ligand
Asn233, Gly182 (main-N) Asn233A, Gly182A (main-N) Stabilises the accumulated negative charge on the beta phosphate leaving group electrostatic stabiliser
Gly457 (main-N) Gly457A (main-N) Backbone NH is proposed to form a hydrogen bond to a gamma phosphate oxygen specifically in the transition state. electrostatic stabiliser
Glu459 Glu459A Acts as a general base as deprotonates a water which will deprotonate the lytic water so that it can nucleophilically attack the gamma phosphate. proton acceptor, proton donor
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

overall reactant used, intermediate formation, bimolecular nucleophilic addition, proton transfer, unimolecular elimination by the conjugate base, intermediate collapse, overall product formed

References

  1. Kiani FA et al. (2015), Curr Opin Struct Biol, 31, 115-123. Advances in quantum simulations of ATPase catalysis in the myosin motor. DOI:10.1016/j.sbi.2015.04.006. PMID:26005996.
  2. Kiani FA et al. (2014), Proc Natl Acad Sci U S A, 111, E2947-E2956. Catalytic strategy used by the myosin motor to hydrolyze ATP. DOI:10.1073/pnas.1401862111. PMID:25006262.
  3. Onishi H et al. (2004), Biochemistry, 43, 3757-3763. On the Myosin Catalysis of ATP Hydrolysis†. DOI:10.1021/bi040002m. PMID:15049682.

Step 1. Glu 459 deprotonates a water which then enables this water to accept a proton from the lytic water. The deprotonated lytic water can then nucleophilically attack the gamma phosphate.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly457A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly182A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand
Glu459A proton acceptor

Chemical Components

overall reactant used, intermediate formation, ingold: bimolecular nucleophilic addition, proton transfer

Step 2. The gamma phosphate accepts a proton from Ser 181 which enables the regeneration of the native protonation state of Glu459 via a third water. Also the transition state collapse on protonation and results in the cleavage of the phosphodiester bond.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Gly182A (main-N) electrostatic stabiliser
Asn233A electrostatic stabiliser
Gly457A (main-N) electrostatic stabiliser
Ser237A metal ligand
Thr186A metal ligand
Ser181A proton acceptor
Glu459A proton donor
Ser181A proton donor, proton relay

Chemical Components

proton transfer, ingold: unimolecular elimination by the conjugate base, intermediate collapse, overall product formed
Download: Image, Marvin File

Step 1. Glu 459 deprotonates a water which then enables this water to accept a proton from the lytic water. The deprotonated lytic water can then nucleophilically attack the gamma phosphate.

Step 2. The gamma phosphate accepts a proton from Ser 181 which enables the regeneration of the native protonation state of Glu459 via a third water. Also the transition state collapse on protonation and results in the cleavage of the phosphodiester bond.

Products.

Contributors

Steven Smith, Gemma L. Holliday, Charity Hornby