Related Experiment Videos
SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold
Jennifer L Martin1, Fiona M McMillan
1Centre for Drug Design and Development, and Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane QLD 4072, Australia. J.Martin@imb.uq.edu.au
Current Opinion in Structural Biology
|December 31, 2002
Summary
S-adenosylmethionine-dependent methyltransferases share a conserved fold but have varied substrate-binding sites. Recent structural studies reveal new proteins with this fold, some lacking methyltransferase activity.
Area of Science:
- Biochemistry and Structural Biology
- Enzymology
Background:
- S-adenosylmethionine-dependent methyltransferases are crucial enzymes with diverse biological roles.
- These enzymes exhibit significant sequence divergence but share a conserved structural fold.
- Understanding the structural basis of their function is key to enzyme engineering and drug discovery.
Purpose of the Study:
- To analyze the structural conservation and variability within the S-adenosylmethionine-dependent methyltransferase fold.
- To investigate the cofactor and substrate binding sites in relation to the conserved fold.
- To characterize newly identified proteins incorporating this structural motif.
Main Methods:
- Comparative structural analysis of S-adenosylmethionine-dependent methyltransferase enzymes.
- Bioinformatic analysis of sequence and structural data.
- Examination of recently determined protein structures.
Main Results:
- A conserved structural fold was identified across S-adenosylmethionine-dependent methyltransferases, despite low sequence identity.
- Cofactor binding residues are poorly conserved but located in a conserved region.
- Substrate-binding regions display extensive variability.
- Recent structural data includes uncharacterized proteins and non-methyltransferase enzymes sharing this fold.
Conclusions:
- The conserved fold provides a versatile scaffold for methyltransferase evolution.
- Variability in substrate binding accommodates diverse biochemical functions.
- The presence of this fold in non-methyltransferases suggests broader evolutionary origins or functions.