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Catalytic Site Atlas

CSA LITERATURE entry for 1h3i

E.C. namehistone-lysine N-methyltransferase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 2.1.1.43
CSA Homologues of 1h3iThere are 10 Homologs
CSA Entries With UniProtID Q8WTS6
CSA Entries With EC Number 2.1.1.43
PDBe Entry 1h3i
PDBSum Entry 1h3i
MACiE Entry M0350

Literature Report

IntroductionHuman methyltransferase SET7/9 catalyses the transfer of a methyl group from the cosubstrate ADOmet to a Lysine residue in Histone H3. Such methylation is used in the regulation of transcription of DNA: it inactivates the DNA towards transcription by creating a silenced chromatin domain. The enzyme displays homology to other SET containing proteins both in humans and in other eukaryotes such as fission yeast (S. cereviseae), with high levels of sequence and structural similarity between the proteins. As a result the SET catalytic domain conserved between the proteins is considered to have the same mechanism in all the methyltransferases.
MechansimProceeds via in-line nucleophilic attack from the target lysine residue in the substrate on the methyl group of the ADOmet molecule, with the lysine activated to act as a nucleophile by deprotonation from a Tyr 335-His 297 diad. This transfers the methyl group to the lysine.
Reaction

Catalytic Sites for 1h3i

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA335335macie:sideChainActs as general base to deprotonate the lysine residue in the target histone such that it can act as a nucleophile.
HisA293293macie:sideChainActs to ensure that Tyr 335 is in the correct protonation state by participating in a proton relay system whereby the proton from the substrate lysine is transfered via Tyr 335 to the residue.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrB335335macie:sideChainActs as general base to deprotonate the lysine residue in the target histone such that it can act as a nucleophile.
HisB293293macie:sideChainActs to ensure that Tyr 335 is in the correct protonation state by participating in a proton relay system whereby the proton from the substrate lysine is transfered via Tyr 335 to the residue.

Literature References

Notes:
Kwon T
Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet.
EMBO J 2003 22 292-303
PubMed: 12514135
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