Daniel E. Almonacid, Ph.D.
Research Summary
Mechanistically diverse enzyme superfamilies are homologous groups of proteins that have evolved from a common ancestor following chemistry-constrained function evolution. Each superfamily member maintains a key mechanistic-step that is mediated by conserved active site residues and cofactors, but has acquired the ability of using that step in different chemical reactions and on different substrates.
On the other hand, functionally analogous enzymes are proteins that have converged into performing the same function, but that are not structurally related as they are the product of different genes. Analogues are therefore not relevant to genomic enzymology and are neglected in many studies. However, from the literature it is clear that convergence of function is more common than divergence.
Up to now enzymes have been commonly classified by using measures of similarity of sequence and structure. Enzyme members of mechanistically diverse superfamilies have also been classified according to the sharing of additional unique residues that perform the step conserved by the superfamily. Recently, however, a new avenue for the classification of enzymes was opened: O’Boyle, myself and other colleagues developed a method that measures similarity of enzymes based upon the explicit mechanism of the reaction catalyzed by the enzyme.
I am currently using measurements of mechanism similarity to study the reactions catalyzed by the members of the mechanistically diverse enzyme superfamilies present in our Structure Function Linkage Database (SFLD), and on functionally analogous enzyme from the MACiE database. I am particularly interested in contrasting the results of clustering of enzymes obtained by the traditional approaches of sequence, structure and active site residue similarities with the method based on mechanism similarity.
Education
Ph.D. 2008, Chemistry
University of Cambridge, Cambridge, U.K.
B.S. with Honors, 2004, Biochemistry
Universidad de Concepción, Concepción, Chile
Publications
The Chemistry of Protein Catalysis.
Gemma L. Holliday, Daniel E. Almonacid, John B. O. Mitchell and Janet M. Thornton,
Journal of Molecular Biology, 372, 1261-1277 (2007)
doi:10.1016/j.jmb.2007.07.034
Using reaction mechanism to measure enzyme similarity.
Noel M. O’Boyle, Gemma L. Holliday, Daniel E. Almonacid and John B. O. Mitchell,
Journal of Molecular Biology, 368, 1484-1499 (2007)
doi:10.1016/j.jmb.2007.02.065
A Semiempirical Approach to the Intra-Phycocyanin and Inter-Phycocyanin Fluorescence Resonance Energy-Transfer Pathways in Phycobilisomes.
Adelio R. Matamala, Daniel E. Almonacid, Maximiliano F. Figueroa, José Martínez-Oyanedel and Marta C. Bunster,
Journal of Computational Chemistry, 28, 1200-1207 (2007)
doi:10.1002/jcc.20628
The structure at 2 A resolution of Phycocyanin from Gracilaria chilensis and the energy transfer network in a PC-PC complex.
Carlos Contreras-Martel, Adelio Matamala, Carola Bruna, German Poo-Caamaño, Daniel Almonacid, Maximiliano Figueroa, José Martínez-Oyanedel and Marta Bunster,
Biophysical Chemistry, 125, 388-396 (2007)
doi:10.1016/j.bpc.2006.09.014
MACiE (Mechanism, Annotation and Classification in Enzymes): novel tools for searching catalytic mechanisms
Gemma L. Holliday, Daniel E. Almonacid, Gail J. Bartlett, Noel M. O'Boyle, James W. Torrance, Peter Murray-Rust, John B. O. Mitchell and Janet M. Thornton,
Nucleic Acids Research, 35, D515-D520 (2007)
doi:10.1093/nar/gkl774
Full text freely available: Open Access click here
MACiE: a database of enzyme reaction mechanisms
Gemma L. Holliday, Gail J. Bartlett, Daniel E. Almonacid, Noel M. O'Boyle, Peter Murray-Rust, Janet M. Thornton and John B.O. Mitchell,
Bioinformatics, 21, 4315-4316 (2005)
doi:10.1093/bioinformatics/bti693
Full text freely available: Open Access click here
