Theoretical study on binding of S100B protein.
S100B protein is one of the factors involved in the down-regulation of tumor suppressor protein p53, a transcription activator that signals for cycle arrest and apoptosis. As the inactivation of normal p53 functions is found in over half of human cancers, restoration of normal p53 functions through the destruction or prevention of S100B--p53 complexes represents a possible approach for the development of anti-cancer drugs. The aim of this work was to propose the S100B binding interface through an examination of the literature and use of molecular modeling (MM) techniques with AutoDock program and the AMBER force field. We propose two residues in the S100B binding pocket (Val56, Phe76) and two residues on the protein surface (Val52, Ala83) are essential for ligand binding. The data presented here indicate that interactions with these four residues are necessary for a reduction in the incidence of the S100B--p53 complex. Additionally, we have tried to explain a mechanism for the action of pentamidine, the best-known S100B ligand, and have proposed two S100B--pentamidine structures. The results presented here may be useful for the efficient design of new S100B ligands.
Gieldon
Artur
A
Protera S. r. l., Viale delle Idee, 22, 50019, Sesto Fiorentino, Fi, Italy. gieldon@proterasrl.com
Mori
Mattia
M
Del Conte
Rebecca
R
D017209:Apoptosis; D001665:Binding Sites; D002453:Cell Cycle; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism*; D010419:Pentamidine / Q000494:pharmacology; D010649:Phenylalanine; D011487:Protein Conformation; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000187:drug effects / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*; D014633:Valine
D008024:Ligands; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016159:Tumor Suppressor Protein p53; D010649:Phenylalanine; D010419:Pentamidine; D014633:Valine
Science. 1994 Jul 15;265(5170):346-55
8023157
J Biomol NMR. 2002 Jul;23(3):255-6
12238603
J Biol Chem. 2004 Aug 6;279(32):34071-7
15178678
J Med Chem. 2004 Oct 7;47(21):5085-93
15456252
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4735-40
15781852
Crit Rev Oncol Hematol. 2006 Feb;57(2):107-21
16326109
Infect Control Hosp Epidemiol. 1991 Jun;12(6):375-82
2071882
Biochem Cell Biol. 1998;76(2-3):324-33
9923701
Arch Neurol. 2006 Jun;63(6):876-80
16769870
Structure. 1998 Feb 15;6(2):211-22
9519411
Biochemistry. 2005 Apr 19;44(15):5690-702
15823027
Neurochem Res. 1999 Sep;24(9):1097-100
10485579
Biochemistry. 2005 May 17;44(19):7305-14
15882069
Biochim Biophys Acta. 2006 Nov;1763(11):1284-97
17010455
Biochemistry. 1998 Feb 17;37(7):1951-60
9485322
J Biol Chem. 1995 Jun 16;270(24):14651-8
7540176
Biochemistry. 2002 Mar 19;41(11):3637-46
11888280
Science. 1991 Jul 5;253(5015):49-53
1905840
Clin Biochem. 2004 Jul;37(7):512-8
15234232
Curr Opin Oncol. 2005 Mar;17(2):167-71
15725923
J Biol Chem. 2001 Sep 14;276(37):35037-41
11454863
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jul 1;61(Pt 7):673-5
16511125
Biochim Biophys Acta. 1996 Oct 11;1313(3):258-67
8898863
Neurochem Res. 2004 Apr;29(4):735-40
15098935
J Mol Biol. 2002 Dec 13;324(5):1003-14
12470955
Nat Struct Biol. 2000 Jul;7(7):570-4
10876243
Biochem Biophys Res Commun. 1965 Jun 9;19(6):739-44
4953930
Cell Mol Neurobiol. 2004 Dec;24(6):833-40
15672683
Curr Top Med Chem. 2005;5(12):1093-108
16248785
Clin Biochem. 2005 May;38(5):433-5
15820773
Biochemistry. 2002 Apr 30;41(17):5421-8
11969402
Biochem J. 2006 Jun 1;396(2):201-14
16683912
Biochem Biophys Res Commun. 1999 Jan 8;254(1):36-41
9920729
Trends Biochem Sci. 1996 Apr;21(4):134-40
8701470
Mol Cell Biol. 1999 Oct;19(10):7168-80
10490652
Mol Carcinog. 2006 Jun;45(6):409-15
16652354
Int J Biochem Cell Biol. 2001 Jul;33(7):637-68
11390274
Science. 2006 Jun 16;312(5780):1650-3
16728594
J Mol Biol. 2002 Mar 22;317(2):279-90
11902843
J Biol Chem. 1986 Aug 25;261(24):11424-8
3733759
EMBO J. 1998 Oct 15;17(20):5913-22
9774336
J Nippon Med Sch. 2006 Apr;73(2):54-64
16641528
Front Biosci. 2002 May 01;7:d1356-68
11991838
Microsc Res Tech. 2003 Apr 15;60(6):614-32
12645009
Biochemistry. 2003 Dec 16;42(49):14416-26
14661952
Cell Mol Biol (Noisy-le-grand). 2005 Sep 05;51(2):201-14
16171556
J Biol Chem. 2003 Feb 21;278(8):6251-7
12480931