3r10 › Citations

Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily.

Lukk T, Sakai A, Kalyanaraman C, Brown SD, Imker HJ, Song L, Fedorov AA, Fedorov EV, Toro R, Hillerich B, Seidel R, Patskovsky Y, Vetting MW, Nair SK, Babbitt PC, Almo SC, Gerlt JA, Jacobson MP
Proc Natl Acad Sci U S A 109 4122-7 (2012)
Related entries: 3iji, 3ijl, 3ijq, 3ik4, 3jva, 3jw7, 3jzu, 3k1g, 3kum, 3q45, 3q4d, 3r0k, 3r0u, 3r11, 3r1z, 3rit, 3ro6

Cited: 38 times
EuropePMC logo PMID: 22392983

Abstract

The rapid advance in genome sequencing presents substantial challenges for protein functional assignment, with half or more of new protein sequences inferred from these genomes having uncertain assignments. The assignment of enzyme function in functionally diverse superfamilies represents a particular challenge, which we address through a combination of computational predictions, enzymology, and structural biology. Here we describe the results of a focused investigation of a group of enzymes in the enolase superfamily that are involved in epimerizing dipeptides. The first members of this group to be functionally characterized were Ala-Glu epimerases in Eschericiha coli and Bacillus subtilis, based on the operon context and enzymological studies; these enzymes are presumed to be involved in peptidoglycan recycling. We have subsequently studied more than 65 related enzymes by computational methods, including homology modeling and metabolite docking, which suggested that many would have divergent specificities;, i.e., they are likely to have different (unknown) biological roles. In addition to the Ala-Phe epimerase specificity reported previously, we describe the prediction and experimental verification of: (i) a new group of presumed Ala-Glu epimerases; (ii) several enzymes with specificity for hydrophobic dipeptides, including one from Cytophaga hutchinsonii that epimerizes D-Ala-D-Ala; and (iii) a small group of enzymes that epimerize cationic dipeptides. Crystal structures for certain of these enzymes further elucidate the structural basis of the specificities. The results highlight the potential of computational methods to guide experimental characterization of enzymes in an automated, large-scale fashion.

Articles - 3r10 mentioned but not cited (1)

  1. Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily. Lukk T, Sakai A, Kalyanaraman C, Brown SD, Imker HJ, Song L, Fedorov AA, Fedorov EV, Toro R, Hillerich B, Seidel R, Patskovsky Y, Vetting MW, Nair SK, Babbitt PC, Almo SC, Gerlt JA, Jacobson MP. Proc Natl Acad Sci U S A 109 4122-4127 (2012)


Reviews citing this publication (8)

  1. Bacterial cell-wall recycling. Johnson JW, Fisher JF, Mobashery S. Ann N Y Acad Sci 1277 54-75 (2013)
  2. Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently. Currin A, Swainston N, Day PJ, Kell DB. Chem Soc Rev 44 1172-1239 (2015)
  3. Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence-Function Space and Genome Context to Discover Novel Functions. Gerlt JA. Biochemistry 56 4293-4308 (2017)
  4. New insights about enzyme evolution from large scale studies of sequence and structure relationships. Brown SD, Babbitt PC. J Biol Chem 289 30221-30228 (2014)
  5. The evolution of enzyme function in the isomerases. Martinez Cuesta S, Furnham N, Rahman SA, Sillitoe I, Thornton JM. Curr Opin Struct Biol 26 121-130 (2014)
  6. Protein production from the structural genomics perspective: achievements and future needs. Almo SC, Garforth SJ, Hillerich BS, Love JD, Seidel RD, Burley SK. Curr Opin Struct Biol 23 335-344 (2013)
  7. Leveraging structure for enzyme function prediction: methods, opportunities, and challenges. Jacobson MP, Kalyanaraman C, Zhao S, Tian B. Trends Biochem Sci 39 363-371 (2014)
  8. Transparency in metabolic network reconstruction enables scalable biological discovery. Heavner BD, Price ND. Curr Opin Biotechnol 34 105-109 (2015)

Articles citing this publication (29)

  1. The Structure-Function Linkage Database. Akiva E, Brown S, Almonacid DE, Barber AE, Custer AF, Hicks MA, Huang CC, Lauck F, Mashiyama ST, Meng EC, Mischel D, Morris JH, Ojha S, Schnoes AM, Stryke D, Yunes JM, Ferrin TE, Holliday GL, Babbitt PC. Nucleic Acids Res 42 D521-30 (2014)
  2. Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily. Akiva E, Copp JN, Tokuriki N, Babbitt PC. Proc Natl Acad Sci U S A 114 E9549-E9558 (2017)
  3. Revealing the hidden functional diversity of an enzyme family. Bastard K, Smith AA, Vergne-Vaxelaire C, Perret A, Zaparucha A, De Melo-Minardi R, Mariage A, Boutard M, Debard A, Lechaplais C, Pelle C, Pellouin V, Perchat N, Petit JL, Kreimeyer A, Medigue C, Weissenbach J, Artiguenave F, De Berardinis V, Vallenet D, Salanoubat M. Nat Chem Biol 10 42-49 (2014)
  4. Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamily. Wallrapp FH, Pan JJ, Ramamoorthy G, Almonacid DE, Hillerich BS, Seidel R, Patskovsky Y, Babbitt PC, Almo SC, Jacobson MP, Poulter CD. Proc Natl Acad Sci U S A 110 E1196-202 (2013)
  5. A transient receptor potential ion channel in Chlamydomonas shares key features with sensory transduction-associated TRP channels in mammals. Arias-Darraz L, Cabezas D, Colenso CK, Alegría-Arcos M, Bravo-Moraga F, Varas-Concha I, Almonacid DE, Madrid R, Brauchi S. Plant Cell 27 177-188 (2015)
  6. Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains. Xu Q, Mengin-Lecreulx D, Liu XW, Patin D, Farr CL, Grant JC, Chiu HJ, Jaroszewski L, Knuth MW, Godzik A, Lesley SA, Elsliger MA, Deacon AM, Wilson IA. mBio 6 e02327-14 (2015)
  7. Urocanate reductase: identification of a novel anaerobic respiratory pathway in Shewanella oneidensis MR-1. Bogachev AV, Bertsova YV, Bloch DA, Verkhovsky MI. Mol Microbiol 86 1452-1463 (2012)
  8. Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis. Bastard K, Perret A, Mariage A, Bessonnet T, Pinet-Turpault A, Petit JL, Darii E, Bazire P, Vergne-Vaxelaire C, Brewee C, Debard A, Pellouin V, Besnard-Gonnet M, Artiguenave F, Médigue C, Vallenet D, Danchin A, Zaparucha A, Weissenbach J, Salanoubat M, de Berardinis V. Nat Chem Biol 13 858-866 (2017)
  9. Catalytic site identification--a web server to identify catalytic site structural matches throughout PDB. Kirshner DA, Nilmeier JP, Lightstone FC. Nucleic Acids Res 41 W256-65 (2013)
  10. A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme family identifies novel members and reveals mechanisms of substrate specificity and quaternary structure organization. Peterhoff D, Beer B, Rajendran C, Kumpula EP, Kapetaniou E, Guldan H, Wierenga RK, Sterner R, Babinger P. Mol Microbiol 92 885-899 (2014)
  11. Participation of the Salmonella OmpD porin in the infection of RAW264.7 macrophages and BALB/c mice. Ipinza F, Collao B, Monsalva D, Bustamante VH, Luraschi R, Alegría-Arcos M, Almonacid DE, Aguayo D, Calderón IL, Gil F, Santiviago CA, Morales EH, Calva E, Saavedra CP. PLoS One 9 e111062 (2014)
  12. Predicting the functions and specificity of triterpenoid synthases: a mechanism-based multi-intermediate docking approach. Tian BX, Wallrapp FH, Holiday GL, Chow JY, Babbitt PC, Poulter CD, Jacobson MP. PLoS Comput Biol 10 e1003874 (2014)
  13. Comparison of topological clustering within protein networks using edge metrics that evaluate full sequence, full structure, and active site microenvironment similarity. Leuthaeuser JB, Knutson ST, Kumar K, Babbitt PC, Fetrow JS. Protein Sci 24 1423-1439 (2015)
  14. Divergent evolution of ligand binding in the o-succinylbenzoate synthase family. Odokonyero D, Ragumani S, Lopez MS, Bonanno JB, Ozerova ND, Woodard DR, Machala BW, Swaminathan S, Burley SK, Almo SC, Glasner ME. Biochemistry 52 7512-7521 (2013)
  15. Letter Evolution of threonine aldolases, a diverse family involved in the second pathway of glycine biosynthesis. Liu G, Zhang M, Chen X, Zhang W, Ding W, Zhang Q. J Mol Evol 80 102-107 (2015)
  16. Genome-Wide Association Study Reveals Candidate Genes Involved in Fruit Trait Variation in Persian Walnut (Juglans regia L.). Bernard A, Crabier J, Donkpegan ASL, Marrano A, Lheureux F, Dirlewanger E. Front Plant Sci 11 607213 (2020)
  17. Discovery of a novel L-lyxonate degradation pathway in Pseudomonas aeruginosa PAO1. Ghasempur S, Eswaramoorthy S, Hillerich BS, Seidel RD, Swaminathan S, Almo SC, Gerlt JA. Biochemistry 53 3357-3366 (2014)
  18. An approach to functionally relevant clustering of the protein universe: Active site profile-based clustering of protein structures and sequences. Knutson ST, Westwood BM, Leuthaeuser JB, Turner BE, Nguyendac D, Shea G, Kumar K, Hayden JD, Harper AF, Brown SD, Morris JH, Ferrin TE, Babbitt PC, Fetrow JS. Protein Sci 26 677-699 (2017)
  19. Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2. Proietti G, Abelak KK, Bishop-Bailey D, Macchiarulo A, Nobeli I. J Mol Model 22 279 (2016)
  20. Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome. Fleischman NM, Das D, Kumar A, Xu Q, Chiu HJ, Jaroszewski L, Knuth MW, Klock HE, Miller MD, Elsliger MA, Godzik A, Lesley SA, Deacon AM, Wilson IA, Toney MD. Protein Sci 23 1060-1076 (2014)
  21. 3,6-Anhydro-L-galactonate cycloisomerase from Vibrio sp. strain EJY3: crystallization and X-ray crystallographic analysis. Lee S, Yun EJ, Kim KH, Kim HY, Choi IG. Acta Crystallogr F Struct Biol Commun 73 511-514 (2017)
  22. Structure-based prediction and identification of 4-epimerization activity of phosphate sugars in class II aldolases. Lee SH, Hong SH, An JU, Kim KR, Kim DE, Kang LW, Oh DK. Sci Rep 7 1934 (2017)
  23. Predicting enzyme-substrate specificity with QM/MM methods: a case study of the stereospecificity of (D)-glucarate dehydratase. Tian B, Wallrapp F, Kalyanaraman C, Zhao S, Eriksson LA, Jacobson MP. Biochemistry 52 5511-5513 (2013)
  24. A new family of bacterial DNA repair proteins annotated by the integration of non-homology, distant homology and structural bioinformatic methods. Mello LV, Rigden DJ. FEBS Lett 586 3908-3913 (2012)
  25. DASP3: identification of protein sequences belonging to functionally relevant groups. Leuthaeuser JB, Morris JH, Harper AF, Ferrin TE, Babbitt PC, Fetrow JS. BMC Bioinformatics 17 458 (2016)
  26. Second-Shell Amino Acid R266 Helps Determine N-Succinylamino Acid Racemase Reaction Specificity in Promiscuous N-Succinylamino Acid Racemase/o-Succinylbenzoate Synthase Enzymes. Truong DP, Rousseau S, Machala BW, Huddleston JP, Zhu M, Hull KG, Romo D, Raushel FM, Sacchettini JC, Glasner ME. Biochemistry 60 3829-3840 (2021)
  27. Biomanufacturing by In Vitro Biotransformation (ivBT) Using Purified Cascade Multi-enzymes. Qin Y, Li Q, Fan L, Ning X, Wei X, You C. Adv Biochem Eng Biotechnol 186 1-27 (2023)
  28. Computational evaluation of factors governing catalytic 2-keto acid decarboxylation. Wu D, Yue D, You F, Broadbelt LJ. J Mol Model 20 2310 (2014)
  29. Crystal structure analysis of 3,6-anhydro-l-galactonate cycloisomerase suggests emergence of novel substrate specificity in the enolase superfamily. Lee S, Kim KH, Kim HY, Choi IG. Biochem Biophys Res Commun 491 217-222 (2017)


Quick links