Document Detail

Divergent evolution of ligand binding in the o-succinylbenzoate synthase family.
MedLine Citation:
PMID:  24060347     Owner:  NLM     Status:  MEDLINE    
Thermobifida fusca o-succinylbenzoate synthase (OSBS), a member of the enolase superfamily that catalyzes a step in menaquinone biosynthesis, has an amino acid sequence that is 22 and 28% identical with those of two previously characterized OSBS enzymes from Escherichia coli and Amycolatopsis sp. T-1-60, respectively. These values are considerably lower than typical levels of sequence identity among homologous proteins that have the same function. To determine how such divergent enzymes catalyze the same reaction, we determined the structure of T. fusca OSBS and identified amino acids that are important for ligand binding. We discovered significant differences in structure and conformational flexibility between T. fusca OSBS and other members of the enolase superfamily. In particular, the 20s loop, a flexible loop in the active site that permits ligand binding and release in most enolase superfamily proteins, has a four-amino acid deletion and is well-ordered in T. fusca OSBS. Instead, the flexibility of a different region allows the substrate to enter from the other side of the active site. T. fusca OSBS was more tolerant of mutations at residues that were critical for activity in E. coli OSBS. Also, replacing active site amino acids found in one protein with the amino acids that occur at the same place in the other protein reduces the catalytic efficiency. Thus, the extraordinary divergence between these proteins does not appear to reflect a higher tolerance of mutations. Instead, large deletions outside the active site were accompanied by alteration of active site size and electrostatic interactions, resulting in small but significant differences in ligand binding.
Denis Odokonyero; Sugadev Ragumani; Mariana S Lopez; Jeffrey B Bonanno; Nicole D S Ozerova; Danae R Woodard; Benjamin W Machala; Subramanyam Swaminathan; Stephen K Burley; Steven C Almo; Margaret E Glasner
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-10-09
Journal Detail:
Title:  Biochemistry     Volume:  52     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-22     Completed Date:  2013-12-12     Revised Date:  2014-10-23    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7512-21     Citation Subset:  IM    
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MeSH Terms
Actinomycetales / enzymology*
Binding Sites
Biological Evolution*
Carbon-Carbon Lyases / chemistry,  genetics,  metabolism*
Catalytic Domain
Escherichia coli / enzymology*
Magnesium / metabolism*
Models, Molecular
Mutagenesis, Site-Directed
Mutation / genetics
Protein Structure, Secondary
Structure-Activity Relationship
Substrate Specificity
Grant Support
Reg. No./Substance:
EC 4.1.-/Carbon-Carbon Lyases; EC 4.1.99.-/o-succinylbenzoic acid synthase; I38ZP9992A/Magnesium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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