The interdigitating loop of the enolase superfamily as a specificity binding determinant or ‘flying buttress’
| Autor: | Stephen L. Bearne |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Protein Conformation Stereochemistry Biophysics Protomer Crystallography X-Ray Biochemistry Catalysis Protein Structure Secondary Substrate Specificity Analytical Chemistry Evolution Molecular 03 medical and health sciences Galactarate dehydratase Protein structure Glucarate dehydratase Amino Acid Sequence Molecular Biology Mannonate dehydratase Binding Sites 030102 biochemistry & molecular biology biology Enolase superfamily Mandelate racemase Lyase 030104 developmental biology Multigene Family Phosphopyruvate Hydratase biology.protein |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1865:619-630 |
| ISSN: | 1570-9639 |
| DOI: | 10.1016/j.bbapap.2017.02.006 |
| Popis: | Background Enzymes of the enolase superfamily (ENS) are mechanistically diverse, yet share a common partial reaction (abstraction of the α-proton from a carboxylate substrate). While the catalytic machinery responsible for the deprotonation reaction has been conserved, divergent evolution has led to numerous ENS members that catalyze different overall reactions. This rich functional diversity has made the ENS an excellent model system for developing the approaches necessary to validate enzyme function. However, enzymes of the ENS also share a common bidomain structure ((β/α)7β-barrel domain and α + β capping domain) which makes validation of function from structural information challenging. Scope of the review This review presents a comparative survey of the structural data obtained over the past decade for enzymes from all seven subgroups that comprise the ENS. Major conclusions Of the seven ENS subgroups (enolase, mandelate racemase (MR), muconate lactonizing enzyme, β-methylaspartate ammonia lyase, d -glucarate dehydratase, d -mannonate dehydratase (ManD), and galactarate dehydratase 2), only enzymes of the MR and ManD subgroups exhibit an additional feature of structural complexity—an interdigitating loop. This loop emanates from one protomer of a homodimeric pair and penetrates into the adjacent, symmetry-related protomer to either contribute a binding determinant to the active site of the adjacent protomer, or act as a ‘flying buttress’ to support residues of the active site. General significance The analysis presented in this review suggests that the interdigitating loop is the only gross structural element that permits functional distinction between ENS subgroups at the tertiary level of protein structure. |
| Databáze: | OpenAIRE |
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