Alteration of oligomeric state and domain architecture is essential for functional transformation between transferase and hydrolase with the same scaffold
Open Access
- 23 September 2009
- journal article
- research article
- Published by Wiley in Protein Science
- Vol. 18 (10), 2060-2066
- https://doi.org/10.1002/pro.218
Abstract
Transferases and hydrolases catalyze different chemical reactions and express different dynamic responses upon ligand binding. To insulate the ligand molecule from the surrounding water, transferases bury it inside the protein by closing the cleft, while hydrolases undergo a small conformational change and leave the ligand molecule exposed to the solvent. Despite these distinct ligand‐binding modes, some transferases and hydrolases are homologous. To clarify how such different catalytic modes are possible with the same scaffold, we examined the solvent accessibility of ligand molecules for 15 SCOP superfamilies, each containing both transferase and hydrolase catalytic domains. In contrast to hydrolases, we found that nine superfamilies of transferases use two major strategies, oligomerization and domain fusion, to insulate the ligand molecules. The subunits and domains that were recruited by the transferases often act as a cover for the ligand molecule. The other strategies adopted by transferases to insulate the ligand molecule are the relocation of catalytic sites, the rearrangement of secondary structure elements, and the insertion of peripheral regions. These findings provide insights into how proteins have evolved and acquired distinct functions with a limited number of scaffolds.Keywords
Funding Information
- Japan Science and Technology Agency, Institute for Bioinformatics Research and Development (JST-BIRD), Ministry of Education, Culture, Sports, Science and Technology, Japan
This publication has 48 references indexed in Scilit:
- The Universal Protein Resource (UniProt) 2009Nucleic Acids Research, 2009
- PiQSi: Protein Quaternary Structure InvestigationStructure, 2007
- Structure of the Escherichia coli DNA Polymerase III ϵ-HOT Proofreading ComplexPublished by Elsevier BV ,2006
- Crystal Structures of Human DcpS in Ligand-free and m7GDP-bound forms Suggest a Dynamic Mechanism for Scavenger mRNA DecappingJournal of Molecular Biology, 2005
- Binding of the anti‐tubercular drug isoniazid to the arylamine N‐acetyltransferase protein from Mycobacterium smegmatisProtein Science, 2005
- Structural Basis for the NAD-dependent Deacetylase Mechanism of Sir2Published by Elsevier BV ,2002
- Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycleJournal of Molecular Biology, 1999
- The relationship between protein structure and function: a comprehensive survey with application to the yeast genomeJournal of Molecular Biology, 1999
- SCOP: A structural classification of proteins database for the investigation of sequences and structuresJournal of Molecular Biology, 1995
- One thousand families for the molecular biologistNature, 1992