title: Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family.
abstract: The rate of protein evolution is determined by a combination of selective pressure on protein function and biophysical constraints on protein folding and structure. Determining the relative contributions of these properties is an unsolved problem in molecular evolution with broad implications for protein engineering and function prediction. As a case study, we examined the structural divergence of the rapidly evolving o-succinylbenzoate synthase (OSBS) family, which catalyzes a step in menaquinone synthesis in diverse microorganisms and plants. On average, the OSBS family is much more divergent than other protein families from the same set of species, with the most divergent family members sharing <15% sequence identity. Comparing 11 representative structures revealed that loss of quaternary structure and large deletions or insertions are associated with the family's rapid evolution. Neither of these properties has been investigated in previous studies to identify factors that affect the rate of protein evolution. Intriguingly, one subfamily retained a multimeric quaternary structure and has small insertions and deletions compared with related enzymes that catalyze diverse reactions. Many proteins in this subfamily catalyze both OSBS and N-succinylamino acid racemization (NSAR). Retention of ancestral structural characteristics in the NSAR/OSBS subfamily suggests that the rate of protein evolution is not proportional to the capacity to evolve new protein functions. Instead, structural features that are conserved among proteins with diverse functions might contribute to the evolution of new functions.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128;
authors.forename: Denis
authors.initials: D
authors.lastname: Odokonyero
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
authors.forename: Ayano
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Departments of Biochemistry and.
authors.forename: Yury
authors.initials: Y
authors.lastname: Patskovsky
authors.affiliation: Departments of Biochemistry and.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Malashkevich
authors.affiliation: Departments of Biochemistry and.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Fedorov
authors.affiliation: Departments of Biochemistry and.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Bonanno
authors.affiliation: Departments of Biochemistry and.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Fedorov
authors.affiliation: Departments of Biochemistry and.
authors.forename: Rafael
authors.initials: R
authors.lastname: Toro
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973;
authors.forename: Rakhi
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128;
authors.forename: Chenxi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128;
authors.forename: Nicole D S
authors.initials: ND
authors.lastname: Ozerova
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore 117597;
authors.forename: Wen Shan
authors.initials: WS
authors.lastname: Yew
authors.affiliation: Lilly Biotechnology Center, San Diego, CA 92121;
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sauder
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973;
authors.forename: Subramanyam
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: BioMaPS Institute for Quantitative Biology,Research Collaboratory for Structural Bioinformatics Protein Data Bank,Center for Integrative Proteomics Research,Rutgers Cancer Institute of New Jersey, andDepartment of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8076.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Burley
authors.affiliation: Departments of Biochemistry andPhysiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461;
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128; margy.glasner@tamu.edu.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Glasner
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D019755:Carbon-Carbon Lyases / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D034301:Deinococcus / Q000201:enzymology / Q000235:genetics; D013293:Enterococcus faecalis / Q000201:enzymology / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D054643:INDEL Mutation; D008087:Listeria / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D010802:Phylogeny; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016963:Thermus thermophilus / Q000201:enzymology / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D019755:Carbon-Carbon Lyases; C052986:o-succinylbenzoic acid synthase
keywords: enolase superfamily; protein structure; protein structure-function relationships