Structure-function analysis of diacylglycerol acyltransferase sequences from 70 organisms

Area of Science:

• Biochemistry and Molecular Biology
• Enzymology
• Bioinformatics

Background:

• Diacylglycerol acyltransferase (DGAT) enzymes are crucial for triacylglycerol (TAG) biosynthesis, a key metabolic pathway.
• Understanding DGATs offers potential for developing transgenic plants and therapeutic strategies for obesity.

Purpose of the Study:

• To identify conserved sequence motifs and amino acid residues in DGAT families.
• To elucidate the structure-function relationship of DGAT enzymes.

Main Methods:

• Database search for 117 DGAT sequences from 70 diverse organisms.
• Phylogenetic analysis to classify DGAT proteins into DGAT1 and DGAT2 subfamilies.
• Sequence alignment to identify conserved amino acid residues and motifs.

Main Results:

• DGATs are integral membrane proteins, with DGAT1s larger than DGAT2s.
• Identified 41 conserved residues in DGAT1s and 16 in DGAT2s, with only two shared across all DGATs.
• Conserved residues are located at carboxyl termini, suggesting catalytic domain localization, and are validated by mutant studies.

Conclusions:

• Conserved motifs and residues in DGAT1 and DGAT2 subfamilies were identified.
• The absence of conserved residues in recently reported isoforms raises questions about functional convergence.
• Findings facilitate DGAT engineering for metabolic applications and inhibitor development for obesity treatment.