Structural analyses of covalent enzyme-substrate analog complexes reveal strengths and limitations of de novo enzyme design

Journal of Molecular Biology

Volumn 415, Issue 3, 2012, Pages 615-625

  Wang, Ling ^a   Althoff, Eric A ^a,b   Bolduc, Jill ^c   Jiang, Lin ^a,d   Moody, James ^a   Lassila, Jonathan K ^e   Giger, Lars ^f   Hilvert, Donald ^f   Stoddard, Barry ^c   Baker, David ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b Arzeda Corporation   (United States)

^c Fred Hutchinson Cancer Research Center   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e STANFORD UNIVERSITY   (United States)

^f ETH ZURICH   (Switzerland)

Author keywords

complex structure; de novo; directed evolution; enzyme design; retro aldolase

Indexed keywords

FRUCTOSE BISPHOSPHATE ALDOLASE; LYSINE; RETRO ALDOLASE RA34.6; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CATALYSIS; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME CONFORMATION; ENZYME SUBSTRATE COMPLEX; PRIORITY JOURNAL; SEQUENCE ANALYSIS; STRUCTURE ANALYSIS;

EID: 84855858058     PISSN: 00222836     EISSN: 10898638     Source Type: Journal    
DOI: 10.1016/j.jmb.2011.10.043     Document Type: Article

References (34)

1. Jiang L., Althoff E.A., Clemente F.R., Doyle L., Rothlisberger D., and Zanghellini A. De novo computational design of retro-aldol enzymes Science 319 2008 1387 1391 (Pubitemid 351354873)
2. Rothlisberger D., Khersonsky O., Wollacott A.M., Jiang L., DeChancie J., and Betker J. Kemp elimination catalysts by computational enzyme design Nature 453 2008 190 195 (Pubitemid 351667979)
3. List B., Barbas C.F., and Lerner R.A. Aldol sensors for the rapid generation of tunable fluorescence by antibody catalysis Proc. Natl Acad. Sci. USA 95 1998 15351 15355 (Pubitemid 29018702)
4. Zanghellini A., Jiang L., Wollacott A.M., Cheng G., Meiler J., and Althoff E.A. New algorithms and an in silico benchmark for computational enzyme design Protein Sci. 15 2006 2785 2794 (Pubitemid 44833759)
5. Bolon D.N., and Mayo S.L. Enzyme-like proteins by computational design Proc. Natl Acad. Sci. USA 98 2001 14274 14279 (Pubitemid 33121382)
6. Siegel J.B., Zanghellini A., Lovick H.M., Kiss G., Lambert A.R., and St Clair J.L. Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction Science 329 2010 309 313
7. Reymond J.L., and Chen Y. Catalytic, enantioselective aldol reaction using antibodies against a quaternary ammonium ion with a primary amine cofactor Tetrahedron Lett. 36 1995 2575 2578
8. Wagner J., Lerner R.A., and Barbas C.F. Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes Science 270 1995 1797 1800 (Pubitemid 26007222)
9. Barbas C.F. III, Heine A., Zhong G., Hoffmann T., Gramatikova S., and Bjornestedt R. Immune versus natural selection: antibody aldolases with enzymic rates but broader scope Science 278 1997 2085 2092 (Pubitemid 28028312)
10. Hilvert D. Critical analysis of antibody catalysis Annu. Rev. Biochem. 69 2000 751 793
11. Hoffmann T., Zhong G., List B., Shabat D., Anderson J., and Gramatikova S. Aldolase antibodies of remarkable scope J. Am. Chem. Soc. 120 1998 2768 2779 (Pubitemid 28191632)
12. Müller M.M., Windsor M.A., Pomerantz W.C., Gellman S.H., and Hilvert D. A rationally designed aldolase foldamer Angew. Chem. Int. Ed. Engl. 48 2009 922 925
13. Johnsson K., Allemann R.K., Widmer H., and Benner S.A. Synthesis, structure and activity of artificial, rationally designed catalytic polypeptides Nature 365 1993 530 532 (Pubitemid 23317772)
14. Hennig M., Darimont B.D., Jansonius J.N., and Kirschner K. The catalytic mechanism of indole-3-glycerol phosphate synthase: crystal structures of complexes of the enzyme from Sulfolobus solfataricus with substrate analogue, substrate, and product J. Mol. Biol. 319 2002 757 766 (Pubitemid 34729448)
15. Kuhlman B., Dantas G., Ireton G.C., Varani G., Stoddard B.L., and Baker D. Design of a novel globular protein fold with atomic-level accuracy Science 302 2003 1364 1368 (Pubitemid 37452172)
16. Fullerton S.W., Griffiths J.S., Merkel A.B., Cheriyan M., Wymer N.J., and Hutchins M.J. Mechanism of the class I KDPG aldolase Bioorg. Med. Chem. 14 2006 3002 3010
17. Wolfenden R., and Snider M.J. The depth of chemical time and the power of enzymes as catalysts Acc. Chem. Res. 34 2001 938 945
18. Bar-Even A., Noor E., Savir Y., Liebermeister W., Davidi D., Tawfik D.S., and Milo R. The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters Biochemistry 50 2011 4402 4410
19. Lassila J.K., Baker D., and Herschlag D. Origins of catalysis by computationally designed retroaldolase enzymes Proc. Natl Acad. Sci. USA 107 2010 4937 4942
20. Zhu X., Tanaka F., Lerner R.A., Barbas C.F., and Wilson I.A. Direct observation of an enamine intermediate in amine catalysis J. Am. Chem. Soc. 131 2009 18206 18207
21. Tanaka F., Fuller R., and Barbas C.F. Development of small designer aldolase enzymes: catalytic activity, folding, and substrate specificity Biochemistry 44 2005 7583 7592 (Pubitemid 40696012)
22. Khersonsky O., Rothlisberger D., Dym O., Albeck S., Jackson C.J., Baker D., and Tawfik D.S. Evolutionary optimization of computationally designed enzymes: Kemp eliminases of the KE07 series J. Mol. Biol. 396 2010 1025 1042
23. Khersonsky O., Rothlisberger D., Wollacott A.M., Murphy P., Dym O., and Albeck S. Optimization of the in-silico-designed Kemp eliminase KE70 by computational design and directed evolution J. Mol. Biol. 407 2011 391 412
24. Lorentzen E., Siebers B., Hensel R., and Pohl E. Mechanism of the Schiff base forming fructose-1,6-bisphosphate aldolase: structural analysis of reaction intermediates Biochemistry 44 2005 4222 4229 (Pubitemid 40403962)
25. Heine A., DeSantis G., Luz J.G., Mitchell M., Wong C.H., and Wilson I.A. Observation of covalent intermediates in an enzyme mechanism at atomic resolution Science 294 2001 369 374 (Pubitemid 32963404)
26. Choi K.H., Shi J., Hopkins C.E., Tolan D.R., and Allen K.N. Snapshots of catalysis: the structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate Biochemistry 40 2001 13868 13875 (Pubitemid 33078855)
27. Kunkel T.A. Rapid and efficient site-specific mutagenesis without phenotypic selection Proc. Natl Acad. Sci. USA 82 1985 488 492 (Pubitemid 15128292)
28. Tanaka F., Fuller R., Shim H., Lerner R.A., and Barbas C.F. Evolution of aldolase antibodies in vitro: correlation of catalytic activity and reaction-based selection J. Mol. Biol. 335 2004 1007 1018 (Pubitemid 38091606)
29. Dess D.B., and Martin J.C. Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones J. Org. Chem. 48 1983 4155 4156
30. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., and Weissig H. The Protein Data Bank Nucleic Acids Res. 28 2000 235 242 (Pubitemid 30047768)
31. Collaborative Computational Project No. 4 The CCP4 suite: programs for protein crystallography Acta Crystallogr., Sect. D: Biol. Crystallogr. 50 1994 760 763
32. McCoy A.J., Grosse-Kunstleve R.W., Adams P.D., Winn M.D., Storoni L.C., and Read R.J. Phaser crystallographic software J. Appl. Crystallogr. 40 2007 658 674 (Pubitemid 47080256)
33. Emsley P., Lohkamp B., Scott W.G., and Cowtan K. Features and development of Coot Acta Crystallogr., Sect. D: Biol. Crystallogr. 66 2010 486 501
34. Vagin A.A., Steiner R.A., Lebedev A.A., Potterton L., McNicholas S., Long F., and Murshudov G.N. REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use Acta Crystallogr., Sect. D: Biol. Crystallogr. 60 2004 2184 2195 (Pubitemid 41742770)