Abstract
Analysis of a set of well characterized enzymes shows that the size of a protein subunit is directly related to the number of unique ligand binding functions described for the particular enzyme. The average size increment is about 5 000 Da per ligand binding function. This value corresponds very well to: (a) the amount of polypeptide chain required to form a stable folded structure, and (b) the size of polypeptide coded by the average exon. This reinforces the hypothesis that exon-coded modules are basic architectural units for proteins. Key predictive elements of this hypothesis are: 1) generally each module has a unique function, such as the ability to bind a specific ligand; 2) the size of an enzyme subunit should be determined by the number of modules required to accomplish the enzyme's biological role.
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Kiehn ED, Holland JJ: Nature 226:544–545, 1970.
Rossman MG, Argos P: Annu Rev Biochem 50:497–532, 1981.
Hopkinson DA, Edwards YH, Harris H: Ann Hum Genet 39:383–397, 1976.
Klotz IM, Darnall DW, Langerman NT, In Neurath H, Hill RC (eds) The Proteins. 3rd ed, Vol 1, 1975, pp 293–410.
Thieme R, Pai EF, Schirmer RH, Schulz GE: J Mol Biol 152:763–782, 1981.
Kantrowitz ER, Pastra-Landis SC, Lipscomb WN: Trends Biochem Sci 5:124–128, 1980.
Wetlaufer DB: Adv Prot Chem 34:61–92, 1981.
Chothia C: Annu Rev Biochem 53:537–572, 1984.
Janin J, Wodak SJ: Prog Biophys Molec Biol 42:21–78, 1983.
Richardson J: Adv Prot Chem 34:167–339, 1981.
Go M: Nature 291:90–94, 1982.
Go M: Proc Natl Acad Sci USA 80:1964–1968, 1983.
Privalov PL: Adv Protein Chem 35:1–104, 1982.
Bennett WS, Huber R: CRC Crit Rev Biochem 15:290–385, 1984.
Lesk AM, Chothia C: J Mol Biol 174:175–191, 1984.
Banerjee A, Levy HR, Levy GC, Chan WW-C: Biochemistry 24:1593–1598, 1985.
Madsen NB, Shechosky S, Fletterick RJ: Biochemistry 22:4460–4465, 1983.
Rossman MG: Phil Trans R Soc Lond B 293:191–203, 1981.
Sols A: Curr Topics Cell Regul 19:77–101, 1981.
Uyeda K: Adv Enzymol 48:193–244, 1979.
Evans PR, Farrants GW, Hudson PJ: Phil Trans R Soc Lond B 293:53–62, 1981.
Naora H, Deacon NJ: Proc Natl Acad Sci USA 70, 6196–6200, 1982.
Gilbert W: Nature 271:501, 1978.
Doolittle WF: Nature 272:581–582, 1978.
Blake CCF: Nature 273:267, 1978.
Artymiuk PJ, Blake CCF, Sippel AE: Nature 290:287–288, 1981.
Blake CCF: Nature 291:616, 1981.
Blake CCF: Nature 306:535–537, 1983.
Jung A, Sippel AE, Grez M, Schütz G: Proc Natl Acad Sci USA 77:5759–5763, 1980.
Stein PJ, Catterall JF, Kristo P, Means AR, O'Malley BW: Cell 21:681–687, 1980.
Sakano N, Rogers JH, Hiippi K, Brack C, Traunecker A, Maki R, Wall R, Tonegawa S: Nature 277:627–633, 1979.
Campbell RD, Porter RR: Proc Nall Acad Sci USA 80:4464–4468, 1983.
Wodak SJ, Janin J: Biochemistry 20:6544–6552, 1981.
Quinto C, Quirago M, Swain WF, Nikovits WF, Jr, Standring N, Picket RC, Valenzuela P, Butter WJ: Proc Natl Acad Sci USA 79:31–35, 1982.
Leicht M, Long GL, Chandra T, Kurachi K, Kidd VJ, Mace M, Jr, Davie EW, Woo SLC: Nature 297:655–660, 1982.
Doolittle RF: Trends Biochem Sci 10:233–237, 1985.
Doolittle RF: Sci American 253:88–99, 1985.
Palm D, Goerl R, Burger KJ: Nature 313:500–503, 1985.
McCarthy AD, Hardie DG: Trends Biochem Sci 9:60–63, 1984.
Robey EA, Schachman HK: Proc Natl Acad Sci USA 82:361–365, 1985.
Krause KL, Volz KW, Lipscomb WN: Proc Natl Acad Sci USA 82:1643–1647, 1985.
Kensington S, Wiegand G, Huber R: J Mol Biol 158:111–152, 1982.
Mayr GW: Eur J Biochem 143:513–520, 1984.
Kruep DA, Dunaway GA: Arch Biochem Biophys 235:504–511, 1984.
Kirkman HN, Gaetani GR: Proc Natl Acad Sci USA 81:4343–4347, 1984.
Matteuzzi M, Bellini T, Bergamini CM, Dallochio F: Biochem Int 10:53–62, 1985.
Ureta T: Comp Biochem Physiol 71B:549–555, 1982.
Sweeney WV, Rabinowitz JC: Ann Rev Biochem 49:139–162, 1980.
Winge DR, Miklossy K-A: J Biol Chem 257:3471–3476, 1982.
Bentley G, Dodson E, Dodson G, Hodkin D, Mercola D: Nature 261:166–168, 1976.
Klee CB, Vanaman TC: Adv Protein Chem 35:213–305, 1982.
Dickerson RE, Geis I: Hemoglobin. Benjamin/Cummings, Menlo Park, CA, 1983.
Nickerson JA, Wells WW: J Biol Chem 259:11297–11304, 1984.
Criss WE, Sapico V, Litwack G: J Biol Chem 245:6346–6351, 1970.
Porter PN, Bull D, Jones OW: Mol Cell Biochem 35:59–64, 1980.
Bresnick E: Methods Enzymol 51:360–365, 1978.
Aronow B, Watts T, Lassetter J, Washtien W, Ullman B: J Biol Chem 259:9035–9043, 1984.
Wickremasinghe RG, Yaxley JC, Hoffbrand V: Biochim Biophys Acta 740:243–248, 1983.
Payne RC, Traut TW: J Biol Chem 258:12485–12488, 1982.
Cardenas JM: Methods Enzymol 90:140- 149, 1982.
Hue L: Adv Enzymol 51:247–331, 1982.
Pilkis SJ, El-Maghrabi MR, Pilkis J, Claus TH: Arch Biochim Biophys 215: 379–381, 1982.
Magni G: Methods Enzymol 51:290–296, 1978.
Tainer JA, Getzoff ED, Beem KM, Richardson JS, Richardson DC: J Mol Biol 160:181–217, 1982.
Thomas CB, Arnold WJ, Kelley WN: J Biol Chem 248:2529–2535, 1983.
Holden JA, Meredith GS, Kelley WN: J Biol Chem 254:6951–6955, 1979.
Holden JA, Kelley WN: J Biol Chem 253:4459–4463, 1978.
Woodward DO: Methods Enzymol 51:202–207, 1978.
Kantrowitz ER, Pastra-Landis SC, Lipscomb WN: Trends Biochem Sci 5:150–153, 1980.
Honzatko RB, Crawford JL, Monaco HL, Ladner JE, Edwards BFP, Evans DR, Warren SG, Wiley DC, Ladner RC, Lipscomb WN: J Mol Biol 160:219–263, 1982.
Becker MA, Meyer LJ, Huisman WH, Lazar C, Adams WB: J Biol Chem 252:3911–3918, 1977.
Mullinax TR, Mock JN, McEvily AJ, Harrison JN: J Biol Chem 257:13233–13239, 1982.
Nagradova NK, Ashmarina LI, Asryants RA, Cherednikova TV, Golovina TO, Muronetz VI: Adv Enz Regul 19:171–204, 1981.
Purich DL, Fromm HJ, Rudolph FB: Adv Enzymol 39:249–326, 1973.
Holmes EW: Adv Enz Regul 19:215–231, 1981.
Leff RL, Itakura M, Udom A, Holmes EW: Adv Enz Regul 22:403–411, 1983.
Fletterick RJ, Madsen NB: Ann Rev Biochem 49:31–61, 1980.
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Traut, T.W. Are proteins made of modules?. Mol Cell Biochem 70, 3–10 (1986). https://doi.org/10.1007/BF00233799
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DOI: https://doi.org/10.1007/BF00233799