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Protein Sci. Mar 1993; 2(3): 366–382.
PMCID: PMC2142374

Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins.


Based on the recently determined X-ray structures of Torpedo californica acetylcholinesterase and Geotrichum candidum lipase and on their three-dimensional superposition, an improved alignment of a collection of 32 related amino acid sequences of other esterases, lipases, and related proteins was obtained. On the basis of this alignment, 24 residues are found to be invariant in 29 sequences of hydrolytic enzymes, and an additional 49 are well conserved. The conservation in the three remaining sequences is somewhat lower. The conserved residues include the active site, disulfide bridges, salt bridges, and residues in the core of the proteins. Most invariant residues are located at the edges of secondary structural elements. A clear structural basis for the preservation of many of these residues can be determined from comparison of the two X-ray structures.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Boel E, Huge-Jensen B, Christensen M, Thim L, Fiil NP. Rhizomucor miehei triglyceride lipase is synthesized as a precursor. Lipids. 1988 Jul;23(7):701–706. [PubMed]
  • Bomblies L, Biegelmann E, Döring V, Gerisch G, Krafft-Czepa H, Noegel AA, Schleicher M, Humbel BM. Membrane-enclosed crystals in Dictyostelium discoideum cells, consisting of developmentally regulated proteins with sequence similarities to known esterases. J Cell Biol. 1990 Mar;110(3):669–679. [PMC free article] [PubMed]
  • Brady L, Brzozowski AM, Derewenda ZS, Dodson E, Dodson G, Tolley S, Turkenburg JP, Christiansen L, Huge-Jensen B, Norskov L, et al. A serine protease triad forms the catalytic centre of a triacylglycerol lipase. Nature. 1990 Feb 22;343(6260):767–770. [PubMed]
  • Brenner S. The molecular evolution of genes and proteins: a tale of two serines. Nature. 1988 Aug 11;334(6182):528–530. [PubMed]
  • Collet C, Nielsen KM, Russell RJ, Karl M, Oakeshott JG, Richmond RC. Molecular analysis of duplicated esterase genes in Drosophila melanogaster. Mol Biol Evol. 1990 Jan;7(1):9–28. [PubMed]
  • Davies DR, Metzger H. Structural basis of antibody function. Annu Rev Immunol. 1983;1:87–117. [PubMed]
  • Delbaere LT, Hutcheon WL, James MN, Thiessen WE. Tertiary structural differences between microbial serine proteases and pancreatic serine enzymes. Nature. 1975 Oct 30;257(5529):758–763. [PubMed]
  • Derewenda ZS, Derewenda U. Relationships among serine hydrolases: evidence for a common structural motif in triacylglyceride lipases and esterases. Biochem Cell Biol. 1991 Dec;69(12):842–851. [PubMed]
  • DiPersio LP, Fontaine RN, Hui DY. Site-specific mutagenesis of an essential histidine residue in pancreatic cholesterol esterase. J Biol Chem. 1991 Mar 5;266(7):4033–4036. [PubMed]
  • Doctor BP, Chapman TC, Christner CE, Deal CD, De La Hoz DM, Gentry MK, Ogert RA, Rush RS, Smyth KK, Wolfe AD. Complete amino acid sequence of fetal bovine serum acetylcholinesterase and its comparison in various regions with other cholinesterases. FEBS Lett. 1990 Jun 18;266(1-2):123–127. [PubMed]
  • Doolittle RF. Proteins. Sci Am. 1985 Oct;253(4):88–99. [PubMed]
  • Fournier D, Bride JM, Karch F, Bergé JB. Acetylcholinesterase from Drosophila melanogaster. Identification of two subunits encoded by the same gene. FEBS Lett. 1988 Oct 10;238(2):333–337. [PubMed]
  • Gibney G, Camp S, Dionne M, MacPhee-Quigley K, Taylor P. Mutagenesis of essential functional residues in acetylcholinesterase. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7546–7550. [PMC free article] [PubMed]
  • Greer J. Comparative modeling methods: application to the family of the mammalian serine proteases. Proteins. 1990;7(4):317–334. [PubMed]
  • Gribskov M, Lüthy R, Eisenberg D. Profile analysis. Methods Enzymol. 1990;183:146–159. [PubMed]
  • Hall LM, Malcolm CA. The acetylcholinesterase gene of Anopheles stephensi. Cell Mol Neurobiol. 1991 Feb;11(1):131–141. [PubMed]
  • Hall LM, Spierer P. The Ace locus of Drosophila melanogaster: structural gene for acetylcholinesterase with an unusual 5' leader. EMBO J. 1986 Nov;5(11):2949–2954. [PMC free article] [PubMed]
  • Han JH, Stratowa C, Rutter WJ. Isolation of full-length putative rat lysophospholipase cDNA using improved methods for mRNA isolation and cDNA cloning. Biochemistry. 1987 Mar 24;26(6):1617–1625. [PubMed]
  • Hui DY, Kissel JA. Sequence identity between human pancreatic cholesterol esterase and bile salt-stimulated milk lipase. FEBS Lett. 1990 Dec 10;276(1-2):131–134. [PubMed]
  • Jbilo O, Chatonnet A. Complete sequence of rabbit butyrylcholinesterase. Nucleic Acids Res. 1990 Jul 11;18(13):3990–3990. [PMC free article] [PubMed]
  • Kawaguchi Y, Honda H, Taniguchi-Morimura J, Iwasaki S. The codon CUG is read as serine in an asporogenic yeast Candida cylindracea. Nature. 1989 Sep 14;341(6238):164–166. [PubMed]
  • Kissel JA, Fontaine RN, Turck CW, Brockman HL, Hui DY. Molecular cloning and expression of cDNA for rat pancreatic cholesterol esterase. Biochim Biophys Acta. 1989 Nov 28;1006(2):227–236. [PubMed]
  • Korza G, Ozols J. Complete covalent structure of 60-kDa esterase isolated from 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rabbit liver microsomes. J Biol Chem. 1988 Mar 5;263(7):3486–3495. [PubMed]
  • Kyger EM, Wiegand RC, Lange LG. Cloning of the bovine pancreatic cholesterol esterase/lysophospholipase. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1302–1309. [PubMed]
  • Lesk AM, Chothia C. How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. J Mol Biol. 1980 Jan 25;136(3):225–270. [PubMed]
  • Levitt M. Conformational preferences of amino acids in globular proteins. Biochemistry. 1978 Oct 3;17(20):4277–4285. [PubMed]
  • Lockridge O, Bartels CF, Vaughan TA, Wong CK, Norton SE, Johnson LL. Complete amino acid sequence of human serum cholinesterase. J Biol Chem. 1987 Jan 15;262(2):549–557. [PubMed]
  • Long RM, Satoh H, Martin BM, Kimura S, Gonzalez FJ, Pohl LR. Rat liver carboxylesterase: cDNA cloning, sequencing, and evidence for a multigene family. Biochem Biophys Res Commun. 1988 Oct 31;156(2):866–873. [PubMed]
  • Mouches C, Pauplin Y, Agarwal M, Lemieux L, Herzog M, Abadon M, Beyssat-Arnaouty V, Hyrien O, de Saint Vincent BR, Georghiou GP, et al. Characterization of amplification core and esterase B1 gene responsible for insecticide resistance in Culex. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2574–2578. [PMC free article] [PubMed]
  • Munger JS, Shi GP, Mark EA, Chin DT, Gerard C, Chapman HA. A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. J Biol Chem. 1991 Oct 5;266(28):18832–18838. [PubMed]
  • Neville LF, Gnatt A, Loewenstein Y, Seidman S, Ehrlich G, Soreq H. Intramolecular relationships in cholinesterases revealed by oocyte expression of site-directed and natural variants of human BCHE. EMBO J. 1992 Apr;11(4):1641–1649. [PMC free article] [PubMed]
  • Nilsson J, Bläckberg L, Carlsson P, Enerbäck S, Hernell O, Bjursell G. cDNA cloning of human-milk bile-salt-stimulated lipase and evidence for its identity to pancreatic carboxylic ester hydrolase. Eur J Biochem. 1990 Sep 11;192(2):543–550. [PubMed]
  • Oakeshott JG, Collet C, Phillis RW, Nielsen KM, Russell RJ, Chambers GK, Ross V, Richmond RC. Molecular cloning and characterization of esterase-6, a serine hydrolase of Drosophila. Proc Natl Acad Sci U S A. 1987 May;84(10):3359–3363. [PMC free article] [PubMed]
  • Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, Schrag J, et al. The alpha/beta hydrolase fold. Protein Eng. 1992 Apr;5(3):197–211. [PubMed]
  • Olson PF, Fessler LI, Nelson RE, Sterne RE, Campbell AG, Fessler JH. Glutactin, a novel Drosophila basement membrane-related glycoprotein with sequence similarity to serine esterases. EMBO J. 1990 Apr;9(4):1219–1227. [PMC free article] [PubMed]
  • Ovnic M, Tepperman K, Medda S, Elliott RW, Stephenson DA, Grant SG, Ganschow RE. Characterization of a murine cDNA encoding a member of the carboxylesterase multigene family. Genomics. 1991 Feb;9(2):344–354. [PubMed]
  • Ozols J. Isolation, properties, and the complete amino acid sequence of a second form of 60-kDa glycoprotein esterase. Orientation of the 60-kDa proteins in the microsomal membrane. J Biol Chem. 1989 Jul 25;264(21):12533–12545. [PubMed]
  • Rubino S, Mann SK, Hori RT, Pinko C, Firtel RA. Molecular analysis of a developmentally regulated gene required for Dictyostelium aggregation. Dev Biol. 1989 Jan;131(1):27–36. [PubMed]
  • Schrag JD, Li YG, Wu S, Cygler M. Ser-His-Glu triad forms the catalytic site of the lipase from Geotrichum candidum. Nature. 1991 Jun 27;351(6329):761–764. [PubMed]
  • Schumacher M, Camp S, Maulet Y, Newton M, MacPhee-Quigley K, Taylor SS, Friedmann T, Taylor P. Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence. Nature. 319(6052):407–409. [PubMed]
  • Shimada Y, Sugihara A, Tominaga Y, Iizumi T, Tsunasawa S. cDNA molecular cloning of Geotrichum candidum lipase. J Biochem. 1989 Sep;106(3):383–388. [PubMed]
  • Sikorav JL, Krejci E, Massoulié J. cDNA sequences of Torpedo marmorata acetylcholinesterase: primary structure of the precursor of a catalytic subunit; existence of multiple 5'-untranslated regions. EMBO J. 1987 Jul;6(7):1865–1873. [PMC free article] [PubMed]
  • Silman I, Futerman AH. Modes of attachment of acetylcholinesterase to the surface membrane. Eur J Biochem. 1987 Dec 30;170(1-2):11–22. [PubMed]
  • Slabas AR, Windust J, Sidebottom CM. Does sequence similarity of human choline esterase, Torpedo acetylcholine esterase and Geotrichum candidum lipase reveal the active site serine residue? Biochem J. 1990 Jul 1;269(1):279–280. [PMC free article] [PubMed]
  • Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 1991 Aug 23;253(5022):872–879. [PubMed]
  • Takagi Y, Morohashi K, Kawabata S, Go M, Omura T. Molecular cloning and nucleotide sequence of cDNA of microsomal carboxyesterase E1 of rat liver. J Biochem. 1988 Nov;104(5):801–806. [PubMed]
  • Winkler FK, D'Arcy A, Hunziker W. Structure of human pancreatic lipase. Nature. 1990 Feb 22;343(6260):771–774. [PubMed]

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