Evolution of protein function, from a structural perspective

Current Opinion in Chemical Biology

Volumn 3, Issue 5, 1999, Pages 548-556

  Todd, Annabelle E ^a   Orengo, Christine A ^a   Thornton, Janet M ^a,b  

^a Biomol Structure and Modelling Unit   (United Kingdom)

^b UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN;

ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME SPECIFICITY; ENZYME STRUCTURE; EVOLUTION; GENE FUNCTION; GENE FUSION; PROTEIN STRUCTURE; REVIEW; STRUCTURE ACTIVITY RELATION;

EID: 0032859140     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(99)00007-1     Document Type: Review

References (47)

1. Acharya KR, Ren JS, Stuart DI, Phillips DC, Fenna RE Crystal structure of human α-lactalbumin at 1.7 Å resolution. J Mol Biol. 221:1991;571-581.
2. Wallace AC, Laskowski RA, Thornton JM Derivation of 3D coordinate templates for searching structural databases: application to the Ser-His-Asp catalytic triads of the serine proteinases and lipases. Protein Sci. 5:1996;1001-1013.
3. Bernstein FC, Koetzle TF, Williams GJB, Meyer EF Jr., Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M The protein data bank: a computer based archival file for macromolecular structures. J Mol Biol. 112:1977;535-542.
4. Murzin AG, Brenner SE, Hubbard T, Chothia C SCOP - A structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 247:1995;536-540.
5. Orengo CA, Michie AD, Jones S, Jones DT, Swindells MB, Thornton JM CATH - a hierarchic classification of protein domain structures. Structure. 5:1997;1093-1108.
6. Enzyme Nomenclature 1992. 1992;Academic Press, New York.
7. Martin ACR, Orengo CA, Hutchinson EG, Jones S, Karmirantzou M, Laskowski RA, Mitchell JBO, Taroni C, Thornton JM Protein folds and functions. Structure. 6:1998;875-884. Statistical analysis of the correlation between protein function and the class, architecture and topology of the structure, based on proteins classified in the CATH domains database. For the enzymes, the EC classification shows little correlation with structure (i.e. enzymes with the same EC number may exhibit different folds and vice versa). For several of the common biological ligands, however, there was a distinct bias towards certain protein classes defined by the stereochemical requirements for binding the ligand. Apart from this class bias though, the binding site could be constituted very differently with different topologies to provide the complementarity in shape and necessary hydrogen bonding, hydrophobic and electrostatic interactions.
8. ••] by incorporating additional data on sequence relatives identified by the program WU-BLAST. The analysis also considered functional annotations from the COGS and MIPS databases. The most significant correlation observed is that for the α/β folds, which are found to be disproportionately associated with enzymes, particularly transferases and hydrolases. α/β folds were also found to be the most versatile folds, particularly the TIM barrel. Interestingly, ancient proteins involved in information processing appeared to have less of a preference for a particular structural class than more modern ones involved in metabolism. Another intriguing suggestion was that nature may favour convergent evolution as a means of reinventing functions rather than extensive divergence, as the authors found more folds associated with functions than functions associated with folds.
9. Orengo CA, Jones DT, Thornton JM Protein superfamilies and domain superfolds. Nature. 372:1994;631-634.
10. Babbitt PC, Gerlt JA Understanding enzyme superfamilies: chemistry as the fundamental determinant in the evolution of new catalytic activities. J Biol Chem. 272:1997;30591-30594.
11. Gerlt JA, Babbitt PC Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysis. Curr Opin Chem Biol. 2:1998;607-612. An excellent review (see [10] also), which discusses several diverse enzyme superfamilies in which the reactions catalysed by members share a common chemical step or reactive intermediate, and so provide valuable insights into the evolution of enzyme catalysis. These include: the enolase superfamily (see text); the crotonase superfamily, in which members stabilise an oxyanion intermediate derived from a Coenzyme A thioester; and the vicinal oxygen chelate superfamily, in which catalysis involves metal-assisted stabilisation of transition states containing anionic oxygen atoms.
12. Bork P, Ouzounis C, Sander C From genome sequences to protein function. Curr Opin Struct Biol. 4:1994;393-403.
13. Bork P, Dandekar T, Diaz-Lazcoz Y, Eisenhaber F, Huynen M, Yuan Y Predicting function: from genes to genomes and back. J Mol Biol. 283:1998;707-725.
14. Richardson JS The anatomy and taxonomy of protein structure. Adv Protein Chem. 34:1981;167-339.
15. Holm L, Sander C An evolutionary treasure: unification of a broad set of amidohydrolases related to urease. Proteins. 28:1997;72-82.
16. Zhang B, Rychlewski L, Pawlowski K, Fetrow JS, Skolnick J, Godzik A From fold predictions to function predictions: automation of functional site conservation analysis for functional genome predictions. Protein, Sci. 8:1999;1104-1115. This paper highlights the importance of considering the conservation of specific functional residues in assessing whether two homologous proteins (based on sequence similarity or fold recognition) actually perform the same function. The authors describe a SITE database for 304 proteins derived by automated extraction from the PDB and SWISSPROT and calculations from coordinates. They suggest that such information can extend the power of sequence approaches by identifying and 'weighting-up' the functionally important residues. For the Escherichia coli genome, the authors make over 100 new fold/function predictions and in addition, they find that the functional residues are not conserved in almost 30% of all fold predictions previously reported, illustrating the functional diversity within fold groups. Such results depend on the quality of the SITE database and the extent to which function changes with active site sequence changes.
17. Karp P What we do not know about sequence analysis and sequence databases. Bioinformatics. 14:1998;753-754.
18. Galperin MY, Walker DR, Koonin EV Analogous enzymes: independent inventions in enzyme evolution. Genome Res. 8:1998;779-790. This paper describes a systematic sequence search through GenBank, to identify non-homologous enzymes with the same EC classification (i.e. unrelated enzymes performing the same function). Using the programs BLAST and PSI-BLAST, they identify 105 such EC numbers, represented by 243 distinct proteins. In 34 of these cases, the proteins were proven to be unrelated, since they are known to adopt different 3D structures. In about one half of the groups of analogous enzymes, they could indentify at least one member that was homologous to a family of enzymes catalysing a different though related reaction, suggesting a route to this diversity. This excellent paper discusses these observations and provides several fascinating biological insights relevant to understanding the evolution of function.
19. Orengo CA, Todd AE, Thornton JM From protein structure to function. Curr Opin Struct Biol. 9:1999;374-382.
20. Ohno S Evolution by gene duplication. 1970;Springer, New York.
21. Jez JM, Bennett MJ, Schlegel BP, Lewis M, Penning TM Comparative anatomy of the aldo-keto reductase superfamily. Biochem J. 326:1997;625-636.
22. Peisach D, Chipman DM, Van Ophem PW, Manning JM, Ringe D Crystallographic study of steps along the reaction pathway of D-amino acid aminotransferase. Biochemistry. 37:1998;4958-4967.
23. Wu G, Fiser A, ter Kuile B, Sali A, Muller M Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase. Proc Natl Acad Sci USA. 96:1999;6285-6290.
24. Perona JJ, Craik CS Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold. J Biol Chem. 28:1997;29987-29990.
25. Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, Schrag Jet al. The α/β hydrolase fold. Protein Eng. 5:1992;197-211.
26. Oue S, Okamoto A, Yano T, Kagamiyama H Redesigning the substrate specificity of an enzyme by cumulative effects of the mutations of non-active site residues. J Biol Chem. 274:1999;2344-2349. Using directed evolution, the substrate specificity of aspartate aminotransferase was altered to valine. Interestingly, of the 17 mutated residues required to change specificity only one makes contact with the substrate, and several are more than 10 Å from the active site.
27. Baker PJ, Waugh ML, Wang X-G, Stillman TJ, Turnbull AP, Engel PC, Rice DW Determinants of substrate specificity in the superfamily of amino acid dehydrogenases. Biochemistry. 36:1997;16109-16115.
28. Demetrius L Role of enzyme-substrate flexibility in catalytic activity: an evolutionary perspective. J Theor Biol. 194:1998;175-194.
29. Petsko GA, Kenyon GL, Gerlt JA, Ringe D, Kozarich JW On the origin of enzymatic species. Trends Biochem Sci. 18:1993;372-376.
30. Babbitt PC, Hasson MS, Wedekind JE, Palmer DRJ, Barrett WC, Reed GH, Rayment I, Ringe D, Kenyon GL, Gerlt JA The enolase superfamily: a general strategy for enzyme-catalysed abstraction of the α-protons of carboxylic acids. Biochemistry. 35:1996;16489-16501.
31. Hasson MS, Schlichting I, Moulai J, Taylor K, Barrett W, Kenyon GL, Babbitt PC, Gerlt JA, Petsko GA, Ringe D Evolution of an enzyme active site: the structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase. Proc Natl Acad Sci USA. 95:1998;10396-10401. This paper presents a detailed structural comparison of the active sites of three members of the enolase superfamily: muconate lactonizing enzyme, mandelate racemase; and enolase. Whilst the metal ligands are conserved in the three enzymes, other catalytic residues exhibit unusual patterns of active site conservation.
32. Gulick AM, Palmer DRJ, Babbitt PC, Gerlt JA, Rayment I Evolution of enzymatic activities in the enolase superfamily: crystal structure of (D)-glucarate dehydratase from Pseudomonas putida. Biochemistry. 37:1998;14358-14368.
33. ••] are observed. Residue conservation is restricted to residues directly interacting with the cofactor. Residues that are located at very different points in the primary sequence, however, contain functional groups that are positionally conserved with respect to the protein fold.
34. Todd AE, Orengo CA, Thornton JM DOMPLOT: a program to generate schematic diagrams of the structural domain organization within proteins, annotated by ligand contacts. Protein Eng. 12:1999;375-379.
35. Orengo CA CORA - topological fingerprints for protein structural families. Protein Sci. 8:1999;699-715.
36. 2. Proc Natl Acad Sci USA. 93:1996;7496-7501.
37. Chothia C One thousand families for the molecular biologist. Nature. 357:1992;543-544.
38. Jones S, Stewart M, Michie A, Swindells MB, Orengo CA, Thornton JM Domain assignment for protein structures using a consensus approach: characterisation and analysis. Protein Sci. 7:1998;233-242.
39. Scrutton NS α/β barrel evolution and the modular assembly of enzymes: emerging trends in the flavin oxidase/dehydrogenase family. BioEssays. 16:1994;115-122.
40. McLachlan AD Gene duplication in the structural evolution of chymotrypsin. J Mol Biol. 128:1979;49-79.
41. +, and the regions at the termini of the conserved core of these proteins differ markedly.
42. Juers DH, Huber RE, Matthews BW Structural comparisons of TIM barrel proteins suggest functional and evolutionary relationships between β-galactosidase and other glycohydrolases. Protein Sci. 8:1999;122-136. Each of the five domains of β-galactosidase from E. coli was scanned against the PDB using three different methods. On the basis of structural similarity and conservation of active site residues of the third, TIM barrel domain, the authors suggest that the protein is a member of the large superfamily of glycosyl hydrolases. The other four domains appear to play a structural role in shaping the active site cleft, conferring specificity for a smaller substrate on this enzyme.
43. Priestle JP, Grutter MG, White JL, Vincent MG, Kania M, Wilson E, Jardetzky TS, Kirschner K, Jansonius JN Three-dimensional structure of the bifunctional enzyme N-(5′-phosphoribosyl) anthranilate isomerase-indole-3-glycerolphosphate synthase from Escherichia coli. Proc Natl Acad Sci USA. 84:1987;5690-5694.
44. Hawkins AR, Lamb HK The molecular biology of multidomain proteins. Eur J Biochem. 232:1995;7-18.
45. Wistow GJ, Mulders JWM, Dejong W The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses. Nature. 326:1987;622-624.
46. Piatigorsky J, Wistow G The recruitment of crystallins: new functions precede gene duplication. Science. 252:1991;1078-1079.
47. Jeffery CJ Moonlighting proteins. Trends Biochem Sci. 24:1999;811. This review discusses proteins that have multiple functions, and the mechanisms by which cells switch between these different roles. Such mechanisms include differential localisation or expression, the use of alternative binding sites, oligomerisation and complex formation. The evolution of multi-functional proteins, and the ways in which moonlighting benefits the cell, are discussed.