[ribulose-bisphosphate carboxylase]-lysine N-methyltransferase

 

Ribulose-1,5-bisphosphate carboxylase-oxygenase large subunit N-methyltransferase enzymes (LSMTs) uses S-adenosyl methionine to methylate Lys 14 of the Rubisco large subunit. Lys 14 is situated in the flexible N-terminal tail of the large subunit, and the precise role of its methylation is not clear. It does not affect the activity of Rubisco but may be involved in targeting other proteins to interact with the tail.

 

Reference Protein and Structure

Sequence
Q43088 UniProt (2.1.1.127, 2.1.1.259) IPR011192 (Sequence Homologues) (PDB Homologues)
Biological species
Pisum sativum (pea) Uniprot
PDB
1mlv - Structure and Catalytic Mechanism of a SET Domain Protein Methyltransferase (2.6 Å) PDBe PDBsum 1mlv
Catalytic CATH Domains
3.90.1410.10 CATHdb (see all for 1mlv)
Click To Show Structure

Enzyme Reaction (EC:2.1.1.127)

S-adenosyl-L-methionine zwitterion
CHEBI:59789ChEBI
+
L-lysinium residue
CHEBI:29969ChEBI
→
S-adenosyl-L-homocysteine zwitterion
CHEBI:57856ChEBI
+
N(6),N(6),N(6)-trimethyl-L-lysine residue
CHEBI:61961ChEBI
+
hydron
CHEBI:15378ChEBI
Alternative enzyme names: Ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (epsilon)N-methyltransferase, Ribulose-bisphosphate-carboxylase/oxygenase N-methyltransferase, Rubisco methyltransferase, RuBisCO methyltransferase, RuBisCO LSMT, S-adenosyl-L-methionine:[3-phospho-D-glycerate-carboxy-lyase (dimerizing)]-lysine 6-N-methyltransferase,

Enzyme Mechanism

Introduction

The ionised form of Tyr 287 deprotonates the -NH3+ group of Lys 14 (on the large subunit of Rubisco). The resulting Lys-NH2 group can then attack the methyl group of the AdoMet sulphonium cation. It is proposed that the pKa of Tyr 287 is depressed (so allowing it to be present in the ionised form which can act as a general base) by the proximity of two positively charged groups: the AdoMet sulfonium cation and the epsilon-ammonium group of the substrate lysine.

Catalytic Residues Roles

UniProt PDB* (1mlv)
Tyr287 Tyr287(243)A Removes proton from Lys14-NH3+ to generate the nucleophilic species Lys14-NH2. activator, 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

proton transfer, overall reactant used, bimolecular nucleophilic substitution, intramolecular nucleophilic substitution, overall product formed, inferred reaction step, native state of enzyme regenerated

References

  1. Trievel RC et al. (2002), Cell, 111, 91-103. Structure and catalytic mechanism of a SET domain protein methyltransferase. DOI:10.2210/pdb1mlv/pdb. PMID:12372303.
  2. Zhang X et al. (2007), Biochemistry, 46, 5505-5514. Catalytic mechanism and product specificity of rubisco large subunit methyltransferase: QM/MM and MD investigations. DOI:10.1021/bi700119p. PMID:17429949.

Step 1. The unprotonated form of Tyr287 deprotonates the ammonium group of Lys14.

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Catalytic Residues Roles

Residue Roles
Tyr287(243)A activator, proton acceptor

Chemical Components

proton transfer, overall reactant used

Step 2. In an SN2 reaction the primary amine group of Lys14 attacks the methyl group of SAM.

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Catalytic Residues Roles

Residue Roles

Chemical Components

ingold: bimolecular nucleophilic substitution

Step 3. Tyr287 is deprotonated.

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Catalytic Residues Roles

Residue Roles
Tyr287(243)A proton donor

Chemical Components

proton transfer

Step 4. Tyr287 deprotonates the secondary ammonium of the Lys14

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Catalytic Residues Roles

Residue Roles
Tyr287(243)A activator, proton acceptor

Chemical Components

proton transfer

Step 5. In an SN2 reaction Lys14 attacks the methyl group of SAM to form a tertiary amine and SAH.

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Catalytic Residues Roles

Residue Roles

Chemical Components

ingold: bimolecular nucleophilic substitution

Step 6. Tyr287 is deprotonated.

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Catalytic Residues Roles

Residue Roles
Tyr287(243)A proton donor

Chemical Components

proton transfer

Step 7. Tyr287 deprotonates the tertiary amine of Lys14.

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Catalytic Residues Roles

Residue Roles
Tyr287(243)A activator, proton acceptor

Chemical Components

proton transfer

Step 8. In an SN2 reaction the tertiary amine of Lys14 attacks SAM, forming the quaternary amine product and SAH.

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Catalytic Residues Roles

Residue Roles

Chemical Components

ingold: intramolecular nucleophilic substitution, overall product formed

Step 9. In an inferred reaction step Tyr287 is deprotonated to regenerate the native state of the enzyme.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Tyr287(243)A proton donor

Chemical Components

proton transfer, inferred reaction step, native state of enzyme regenerated
Download: Image, Marvin File

Step 1. The unprotonated form of Tyr287 deprotonates the ammonium group of Lys14.

Step 2. In an SN2 reaction the primary amine group of Lys14 attacks the methyl group of SAM.

Step 3. Tyr287 is deprotonated.

Step 4. Tyr287 deprotonates the secondary ammonium of the Lys14

Step 5. In an SN2 reaction Lys14 attacks the methyl group of SAM to form a tertiary amine and SAH.

Step 6. Tyr287 is deprotonated.

Step 7. Tyr287 deprotonates the tertiary amine of Lys14.

Step 8. In an SN2 reaction the tertiary amine of Lys14 attacks SAM, forming the quaternary amine product and SAH.

Step 9. In an inferred reaction step Tyr287 is deprotonated to regenerate the native state of the enzyme.

Products.

Contributors

Steven Smith, Gemma L. Holliday, Amelia Brasnett