Abstract
Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large percentage of them have not been characterized at the functional level. The structural information has provided valuable functional insights on some of these proteins, through careful structural analyses, serendipity, and structure-guided functional screening. Some of the success stories based on structures solved at the Northeast Structural Genomics Consortium (NESG) are reported here. These include a novel methyl salicylate esterase with important role in plant innate immunity, a novel RNA methyltransferase (H. influenzae yggJ (HI0303)), a novel spermidine/spermine N-acetyltransferase (B. subtilis PaiA), a novel methyltransferase or AdoMet binding protein (A. fulgidus AF_0241), an ATP:cob(I)alamin adenosyltransferase (B. subtilis YvqK), a novel carboxysome pore (E. coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP_1951), and a 12-stranded β-barrel with a novel fold (V. parahaemolyticus VPA1032).
Similar content being viewed by others
References
Chandonia J-M, Brenner SE (2006) Science 311:347
Terwilliger TC (2004) Nature Struct Mol Biol 11:296
Liu J, Montelione GT, Rost B (2007) Nat Biotech in press
Yang Z, Savchenko A, Yakunin A, Zhang R, Edwards A, Arrowsmith C, Tong L (2003) J Biol Chem 278:8804
Forouhar F, Shen J, Xiao R, Acton TB, Montelione GT, Tong L (2003) Proteins 53:329
Forouhar F, Lee I, Benach J, Kulkarni K, Xiao R, Acton TB, Montelione GT, Tong L (2004) J Biol Chem 279:13148
Cort JR, Chiang Y, Zheng D, Montelione GT, Kennedy MA (2002) Proteins 48:733
Blankenfeldt W, Kuzin AP, Skarina T, Korniyenko Y, Tong L, Beyer P, Janning P, Thomashow LS, Mavrodi DV (2004) Proc Natl Acad Sci USA 101:16431
Forouhar F, Yang Y, Kumar D, Yang C, Fridman Y, Park SW, Chiang Y, Acton TB, Montelione GT, Pichersky E, Klessig DF, Tong L (2005) Proc Natl Acad Sci USA 102:1773
Forouhar F, Lee I, Vujcic S, Vujcic J, Shen J, Vorobiev SM, Xiao R, Acton TB, Montelione GT, Porter CW, Tong L (2005) J Biol Chem 280:40328
Forouhar F, Anderson JLR, Mowat CG, Vorobiev SM, Hussain A, Abashidze M, Bruckmann C, Thackray SJ, Seetharaman J, Tucker T, Xiao R, Ma L-C, Zhao L, Acton TB, Montelione GT, Chapman SK, Tong L (2007) Proc Natl Acad Sci USA 104:473
Wunderlich Z, Acton TB, Liu J, Kornhaber G, Everett J, Carter P, Lan N, Echols N, Gerstein M, Rost B, Montelione GT (2004) Proteins 56:181
Acton TB, Gunsalus K, Xiao R, Ma L, Aramini J, Baron MC, Chiang Y, Clement T, Cooper B, Denissova N, Douglas S, Everett JK, Palacios D, Paranji RH, Shastry R, Wu M, Ho C-H, Shih L, Swapna GVT, Wilson M, Gerstein M, Inouye M, Hunt JF, Montelione GT (2005) Methods Enzymol 394:210
Jansson M, Li Y-C, Jendeberg L, Anderson S, Montelione GT, Nilsson B (1996) J Biomol NMR 7:131
Doublie S, Kapp U, Aberg A, Brown K, Strub K, Cusack S (1996) FEBS Lett 384:219
Luft JR, Collins RJ, Fehrman NA, Lauricella AM, Veatch CK, DeTitta GT (2003) J Struct Biol 142:170
Otwinowski Z, Minor W (1997) Method Enzymol 276:307
Weeks CM, Miller R (1999) J Appl Cryst 32:120
Sheldrick GM (1990) Acta Cryst A46:467
Terwilliger TC (2003) Meth Enzymol 374:22
Jogl G, Tao X, Xu Y, Tong L (2001) Acta Cryst D57:1127
Jones TA, Zou JY, Cowan SW, Kjeldgaard M (1991) Acta Cryst A47:110
McRee DE (1999) J Struct Biol 125:156
Emsley P, Cowtan KD (2004) Acta Cryst D60:2126
Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang J-S, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL (1998) Acta Cryst D54:905
Du H, Klessig DF (1997) Plant Phyisol 113:1319
Kumar D, Klessig DF (2003) Proc Natl Acad Sci USA 100:16101
Nureki O, Shirouzu M, Hashimoto K, Ishitani R, Terada T, Tamakoshi M, Oshima T, Chijimatsu M, Takio K, Vassylyev DG, Shibata T, Inoue Y, Kuramitsu S, Yokoyama S (2002) Acta Cryst D58:1129
Zarembinski TI, Kim Y, Peterson K, Christendat D, Dharamsi A, Arrowsmith CH, Edwards A, Joachimiak A (2003) Proteins 50:177
Lim K, Zhang H, Tempczyk A, Krajewski W, Bonander N, Toedt J, Howard A, Eisenstein E, Herzberg O (2003) Proteins 51:56
Basturea GN, Rudd KE, Deutscher MP (2006) RNA 12:426
Honjo M, Nakayama A, Fukazawa K, Kawamura K, Ando K, Hori M, Furutani Y (1990) J Bacteriol 172:1783
Liao D-I, Wawrzak Z, Calabrese JC, Viitanen PV, Jordan DB (2001) Structure 9:399
Gerhardt S, Schott AK, Kairies N, Cushman M, Illarionov B, Eisenreich W, Bacher A, Huber R, Steinbacher S, Fischer M (2002) Structure 10:1371
Holm L, Sander C (1993) J Mol Biol 233:123
Saridakis V, Yakunin A, Xu X, Anandakumar P, Pennycooke M, Gu J, Cheung F, Lew JM, Sanishvili R, Joachimiak A, Arrowsmith CH, Christendat D, Edwards AM (2004) J Biol Chem 279:23646
Schubert HL, Hill CP (2006) Biochem 45:15188
St Maurice M, Mera PE, Taranto MP, Sesma F, Escalante-Semerena JC, Rayment I (2007) J Biol Chem 282:2596
Kerfeld CA, Sawaya MR, Tanaka S, Nguyen CV, Phillips M, Beeby M, Yeates TO (2005) Science 309:936
Kofoid E, Rappleye C, Stojiljkovic I, Roth J (1999) J Bacteriol 181:5317
Reina-San-Martin B, Degrave W, Rougeot C, Cosson A, Chamond N, Cordeiro-da-Silva A, Arala-Chaves M, Coutinho A, Minoprio P (2000) Nat Med 6:890
Buschiazzo A, Goytia M, Schaeffer F, Degrave W, Shepard W, Gregoire C, Chamond N, Cosson A, Berneman A, Coatnoan N, Alzari PM, Minoprio P (2006) Proc Natl Acad Sci USA 103:1705
Yang W, Ni L, Somerville RL (1993) Proc Natl Acad Sci USA 90:5796
Grandori R, Khalifah P, Boice JA, Fairman R, Giovanielli K, Carey J (1998) J Biol Chem 273:20960
Gorman J, Shapiro L (2005) Prot Sci 14:3004
Bladergroen MR, Badelt K, Spaink HP (2003) Mol Plant Microbe Interact 16:53
Kim YR, Lee SE, Kim CM, Kim SY, Shin EK, Shin DH, Chung SS, Choy HE, Progulske-Fox A, Hillman JD, Handfield M, Rhee JH (2003) Infect Immun 71:5461
Binkowski TA, Joachimiak A, Liang J (2005) Prot Sci 14:2972
Glaser F, Morris RJ, Najmanovich RJ, Laskowski RA, Thornton JM (2006) Proteins 62:479
Kraulis PJ (1991) J Appl Cryst 24:946
Merritt EA, Bacon DJ (1997) Meth Enzymol 277:505
Acknowledgements
We thank Randy Abramowitz and John Schwanof at the NSLS for setting up the beamlines; G. DeTitta of Hauptman Woodward Research Institute for crystallization screening. This research was supported by grants from the Protein Structure Initiative of the National Institutes of Health (P50 GM62413 and U54 GM074958).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Forouhar, F., Kuzin, A., Seetharaman, J. et al. Functional insights from structural genomics. J Struct Funct Genomics 8, 37–44 (2007). https://doi.org/10.1007/s10969-007-9018-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10969-007-9018-3