Large-Scale Analysis Exploring Evolution of Catalytic Machineries and Mechanisms in Enzyme Superfamilies. Issue 2 (29th January 2016)

• Record Type: Journal Article
• Authors: Furnham, Nicholas; Dawson, Natalie L.; Rahman, Syed A.; Thornton, Janet M.; Orengo, Christine A.
• Is Part Of: Journal of molecular biology. Volume 428:Issue 2 Part A(2016:Jan. 15)
• Page Start: 253
• Page End: 267
• Publication Date: 2016-01-29
• Subjects: EC Enzyme Commission -- IUBMB International Union of Biochemistry and Molecular Biology -- CSA Catalytic Site Atlas -- SSG structurally similar groups -- TIM triosephosphate isomerase -- CMSS Catalytic Machinery Similarity Score -- NP normalised proportion -- GOX glycolate oxidase -- FCB flavocytochrome b2 -- FMN flavin mononucleotide; protein domain evolution -- enzyme function evolution -- catalytic residues -- protein domain superfamilies -- enzyme reaction chemistry; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2015.11.010
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Enzymes, as biological catalysts, form the basis of all forms of life. How these proteins have evolved their functions remains a fundamental question in biology. Over 100 years of detailed biochemistry studies, combined with the large volumes of sequence and protein structural data now available, means that we are able to perform large-scale analyses to address this question. Using a range of computational tools and resources, we have compiled information on all experimentally annotated changes in enzyme function within 379 structurally defined protein domain superfamilies, linking the changes observed in functions during evolution to changes in reaction chemistry. Many superfamilies show changes in function at some level, although one function often dominates one superfamily. We use quantitative measures of changes in reaction chemistry to reveal the various types of chemical changes occurring during evolution and to exemplify these by detailed examples. Additionally, we use structural information of the enzymes active site to examine how different superfamilies have changed their catalytic machinery during evolution. Some superfamilies have changed the reactions they perform without changing catalytic machinery. In others, large changes of enzyme function, in terms of both overall chemistry and substrate specificity, have been brought about by significant changes in catalytic machinery. Interestingly, in some superfamilies, relatives perform similar functions but with different catalytic machineries. This analysis highlights characteristics of functional evolution across a wide range of superfamilies, providing insights that will be useful in predicting the function of uncharacterised sequences and the design of new synthetic enzymes. Graphical abstract: Highlights: Examining how enzyme function evolves using sequence, structure, and reaction mechanism data. Quantifying changes in reaction mechanisms reveals how function has diverged in many superfamilies. Homologous domains frequently use different catalytic residues, which sometimes perform the same enzyme chemistry. This large-scale analysis has significance in protein function prediction and enzyme design.