Interactions between proteins, drugs, water and B-DNA minor groove have been analyzed in crystal structures of 60 protein-DNA and 14 drug-DNA complexes. It was found that only purine N3, pyrimidine O2, guanine N2 and deoxyribose O4' are involved in the interactions, and that contacts to N3 and O2 are most frequent and more polar than contacts to O4'. Many protein contacts are mediated by water, possibly to increase the DNA effective surface. Fewer water-mediated contacts are observed in drug complexes. The distributions of ligands around N3 are significantly more compact than around O2, and distributions of water molecules are the most compact. Distributions around O4' are more diffuse than for the base atoms but most distributions still have just one binding site. Ligands bind to N3 and O2 atoms in analogous positions, and simultaneous binding to N3 and N2 in guanines is extremely rare. Contacts with two consecutive nucleotides are much more frequent than base-sugar contacts within one nucleotide. The probable reason for this is the large energy of deformation of hydrogen bonds for the one nucleotide motif. Contacts of Arg, the most frequent amino acid ligand, are stereochemically indistinguishable from the binding of the remaining amino acids except asparagine (Asn) and phenylalanine (Phe). Asn and Phe bind in distinct ways, mostly to a deformed DNA, as in the complexes of TATA-box binding proteins. DNA deformation concentrates on dinucleotide regions with a distinct deformation of the delta and epsilon backbone torsion angles for the Asn and delta, epsilon, zeta and chi for the Phe-contacted regions.

Faculty of Mathematics and Physics Charles University Ke Karlovu 5 Prague Czech Republic

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Wemmer D.E. and Dervan,P.B. (1997) Targeting the minor groove of DNA. Curr. Opin. Struct. Biol., 7, 355–361. PubMed

Reddy B.S.P., Sondhi,S.M. and Lown,J.W. (1999) Synthetic DNA minor-groove binding drugs. Pharmacol. Ther., 84, 1–111. PubMed

Neidle S. (2001) DNA minor-groove recognition by small molecules. Natural Prod. Rep., 18, 291–309. PubMed

Dervan P.B. and Buerli,R.W. (1999) Sequence-specific DNA recognition by polyamides. Curr. Opin. Chem. Biol., 3, 688–693. PubMed

Neidle S. (1997) Crystallographic insights into DNA minor groove recognition by drugs. Biopolymers, 44, 105–121.

Tabernero L., Bella,J. and Alemán,C. (1996) Hydrogen bond geometry in DNA-minor groove binding drug complexes. Nucleic Acids Res., 24, 3458–3466. PubMed PMC

Mandel-Gutfreund Y., Schueler,O. and Margalit,H. (1995) Comprehensive analysis of hydrogen bonds in regulatory protein DNA-complexes: in search of common principles. J. Mol. Biol., 253, 370–382. PubMed

Jones S., van Heyningen,P., Berman,H.M. and Thornton,J.M. (1999) Protein–DNA interactions: a structural analysis. J. Mol. Biol., 287, 877–896. PubMed

Nadassy K., Wodak,S.J. and Janin,J. (1999) Structural features of protein-nucleic acid recognition sites. Biochemistry, 38, 1999–2017. PubMed

Pabo C.O. and Nekludova,L. (2000) Geometric analysis and comparison of protein–DNA interfaces: why is there no simple code for recognition? J. Mol. Biol., 301, 597–624. PubMed

Luscombe N.M., Laskowski,R.A. and Thornton,J.M. (2001) Amino acid-base interactions: a three-dimensional analysis of protein–DNA interactions at an atomic level. Nucleic Acids Res., 29, 2860–2874. PubMed PMC

Suzuki M., Brenner,S.E., Gerstein,M. and Yagi,N. (1995) DNA recognition code of transcription factors. Protein Eng., 8, 319–328. PubMed

Gray S. (2001) Rules for 3D protein–DNA interactions. Trends Genet., 17, 494–494.

Berman H.M., Olson,W.K., Beveridge,D.L., Westbrook,J., Gelbin,A., Demeny,T., Hsieh,S.-H., Srinivasan,A.R. and Schneider,B. (1992) The Nucleic Acid Database—a comprehensive relational database of three-dimensional structures of nucleic acids. Biophys. J., 63, 751–759. PubMed PMC

Cohen D., Vadaparty,K. and Dickinson,B. (1995) Efficient algorithms for distance queries in macromolecular structure databases. University of Pittsburgh, Pittsburgh, PA.

Clowney L., Jain,S.C., Srinivasan,A.R., Westbrook,J., Olson,W.K. and Berman,H.M. (1996) Geometric parameters in nucleic acids: nitrogenous bases. J. Am. Chem. Soc., 118, 509–518.

Jones T.A., Zou,J.-Y., Cowan,S.W. and Kjeldgaard,M. (1991) Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A, 47, 110–119. PubMed

Schneider B., Cohen,D.M., Schleifer,L., Srinivasan,A.R., Olson,W.K. and Berman,H.M. (1993) A systematic method for studying the spatial distribution of water molecules around nucleic acid bases. Biophys. J., 65, 2291–2303. PubMed PMC

Schneider B. and Berman,H.M. (1995) Hydration of the DNA bases is local. Biophys. J., 69, 2661–2669. PubMed PMC

Frisch M.J., Trucks,G.W., Schlegel,H.B., Gill,P.M.W., Johnson,B.G., Robb,M.A., Cheeseman,J.R., Keith,T., Petersson,G.A., Montgomery,J.A., Raghavachari,K., Al-Laham,M.A., Zakrzewski,V.G., Ortiz,J.V., Foresman,J.B., Cioslowski,J., Stefanov,B.B., Nanayakkara,A., Challacombe,M., Peng,C.Y., Ayala,P.Y., Chen,W., Wong,M.W., Andres,J.L., Replogle,E.S., Gomperts,R., Martin,R.L., Fox,D.J., Binkley,J.S., Defries,D.J., Baker,J., Stewart,J.P., Head-Gordon,M., Gonzalez,C. and Pople,J.A. (1995) Gaussian 94, Revision E.2. Gaussian Inc., Pittsburgh, PA.

Woda J., Schneider,B., Patel,K., Mistry,K. and Berman,H.M. (1998) An analysis of the relationship between hydration and protein–DNA interactions. Biophys. J., 75, 2170–2177. PubMed PMC

Juo Z.S., Chiu,T.K., Leiberman,P.M., Baikalov,I., Berk,A.J. and Dickerson,R.E. (1996) How proteins recognize the TATA box. J. Mol. Biol., 261, 239–254. PubMed

Kim J.L. and Burley,S.K. (1994) 1.9 Å Resolution refined structure of TBP recognizing the minor groove of TATAAAAG. Nature Struct. Biol., 1, 638–653. PubMed

Kim Y., Geiger,J.H., Hahn,S. and Sigler,P.B. (1993) Crystal structure of a yeast TBP/TATA-box complex. Nature, 365, 512–520. PubMed

Kosa P.F., Ghosh,G., Dedecker,B.S. and Sigler,P.B. (1997) The 2.1-Å crystal structure of an archaeal preinitiation complex: TATA-box-binding protein/transcription factor (II)B core/TATA-box. Proc. Natl Acad. Sci. USA, 94, 6042–6047. PubMed PMC

Kim Y., Grable,J.C., Love,R., Greene,P.J. and Rosenberg,J.M. (1990) Refinement of EcoRI endonuclease crystal structure: a revised protein chain tracing. Science, 249, 1307–1309. PubMed

Weston S.A., Lahm,A. and Suck,D. (1992) X-ray structure of the DNase I-d(GGTATACC)2 complex at 2.3 Å resolution. J. Mol. Biol., 226, 1237–1256. PubMed

Lahm A. and Suck,D. (1991) DNase I-induced DNA conformation. 2 Å Structure of a DNase I–octamer complex. J. Mol. Biol., 221, 645–667. PubMed

Feng J.A., Johnson,R.C. and Dickerson,R.E. (1994) Hin recombinase bound to DNA—the origin of specificity in major and minor groove interactions. Science, 263, 348–355. PubMed

Buckle A.M. and Fersht,A.R. (1994) Subsite binding in an RNase: structure of a barnase-tetranucleotide complex at 1.76 Å resolution. Biochemistry, 33, 1644–1653. PubMed

Birdsall D.L. and McPherson,A. (1992) Crystal structure disposition of thymidylic acid tetramer in complex with ribonuclease A. J. Biol. Chem., 267, 22230–22236. PubMed

Fontecilla-Camps J.C., de Llorens,R., le Du,M.H. and Cuchillo,C.M. (1994) Crystal structure of the ribonuclease A–d(ApTpApApG) complex. Direct evidence for extended substrate recognition. J. Biol. Chem., 269, 21526–21531. PubMed

Sawaya M.R., Prasad,R., Wilson,S.H., Kraut,J. and Pelletier,H. (1997) Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism. Biochemistry, 36, 11205–11215. PubMed

van Pouderoyen G., Ketting,R.F., Perrakis,A., Plasterk,R.H.A. and Sixma,T.K. (1997) Crystal structure of the specific DNA-binding domain of Tc3 transposase of C.elegans in complex with transposon DNA. EMBO J., 16, 6044–6054. PubMed PMC

Doublié S., Tabor,S., Richardson,C. and Ellenberger,T. (1998) Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Nature, 391, 251–258. PubMed

Brautigam C.A. and Steitz,T.A. (1998) Structural principles for the inhibition of the 3′–5′ exonuclease activity of Escherichia coli DNA polymerase I by phosphorothioates. J. Mol. Biol., 277, 363–377. PubMed

Horton N.C., Newberry,K.J. and Perona,J.J. (1998) Metal ion-mediated substance-assisted catalysis in type II restriction endonucleases. Proc. Natl Acad. Sci. USA, 95, 13489–13494. PubMed PMC

Kostrewa D. and Winkler,F.K. (1995) Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 Å resolution. Biochemistry, 34, 683–696. PubMed

Redinbo M.R., Stewart,L., Kuhn,P., Champoux,J.J. and Hol,W.G.J. (1998) Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science, 279, 1504–1513. PubMed

Flick K.E., Jurica,M.S., Monnat,R.J. and Stoddard,B.L. (1998) DNA binding and cleavage by the nuclear intron-encoded homing endonuclease I-PpoI. Nature, 394, 96–101. PubMed

Martin A.M., Sam,M.D., Reich,N.O. and Perona,J.J. (1999) Structural and energetic origins of indirect readout in site-specifc DNA cleavage by a restriction endonuclease. Nature Struct. Biol., 6, 269–277. PubMed

Newman M., Strzelecka,T., Dorner,L.F., Schildkraut,I. and Aggarwal,A.K. (1995) Structure of BamHI endonuclease bound to DNA: partial folding and unfolding on DNA binding. Science, 269, 656–663. PubMed

Wilson D.S., Guenther,B., Desplan,C. and Kuriyan,J. (1995) High resolution crystal structure of a paired (Pax) class cooperative homeodomain dimer on DNA. Cell, 82, 709–719. PubMed

Savva R., McAuley-Hecht,K., Brown,T. and Pearl,L. (1995) The structural basis of specific base-excision repair by uracil-DNA glycosylase. Nature, 373, 487–493. PubMed

Wang J., Yu,P., Lin,T.C., Konigsberg,W.H. and Steitz,T.A. (1996) Crystal structures of an NH2-terminal fragment of T4 DNA polymerase and its complexes with single-stranded DNA and with divalent metal ions. Biochemistry, 35, 8110–8119. PubMed

Perona J.J. and Martin,A.M. (1997) Conformational transitions and structural deformability of EcoRV endonuclease revealed by crystallographic analysis. J. Mol. Biol., 273, 207–225. PubMed

Kumar S., Horton,J.R., Jones,G.D., Walker,R.T., Roberts,R.J. and Cheng,X. (1997) DNA containing 4′-thio-2′-deozycytidine inhibits methylation by HhaI methyltransferase. Nucleic Acids Res., 25, 2773–2783. PubMed PMC

Bochkarev A., Pfuetzner,R.A., Edwards,A.M. and Frappier,L. (1997) Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature, 385, 176–181. PubMed

Aggarwal A.K., Rodgers,D.W., Drottar,M., Ptashne,M. and Harrison,S.C. (1988) Recognition of a DNA operator by the repressor of phage 434: a view at high resolution. Science, 242, 899–907. PubMed

Otwinowski Z., Schevitz,R.W., Zhang,R.-G., Lawson,C.L., Joachimiak,A., Marmorstein,R.Q., Luisi,B.F. and Sigler,P.B. (1988) Crystal structure of trp repressor/operator complex at atomic resolution. Nature, 335, 321–329. PubMed

Shimon L.J.W. and Harrison,S.C. (1993) The phage 434 OR2/R1-69 complex at 2.5 Å resolution. J. Mol. Biol., 232, 826–838. PubMed

Lawson C.L. and Carey,J. (1993) Tandem binding in crystals of a trp repressor/operator half-site complex. Nature, 366, 178–182. PubMed

Rodgers D.W. and Harrison,S.C. (1993) The complex between phage 434 repression DNA-binding domain and operator site Or3: structural differences between consensus and non-consensus half-sites. Structure, 1, 227–240. PubMed

Xu W.G., Rould,M.A., Jun,S., Desplan,C. and Pabo,C.O. (1995) Crystal structure of a paired domain-DNA complex at 2.5 Å resolution reveals structural basis for Pax developmental mutations. Cell, 80, 639–650. PubMed

Rastinejad F., Perlmann,T., Evans,R.M. and Sigler,P.B. (1995) Structural determinants of nuclear receptor assembly on DNA direct repeats. Nature, 375, 203–211. PubMed

Cho Y., Gorina,S., Jeffrey,P.D. and Pavletich,N.P. (1994) Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science, 265, 346–355. PubMed

Jacobson E.M., Li,P., Leon-del-Rio,A., Rosenfeld,M.G. and Aggarwal,A.K. (1997) Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev., 11, 198–212. PubMed

Tan S. and Richmond,T.J. (1998) Crystal structure of the yeast MAT alpha 2/MCM1/DNA ternary complex. Nature, 391, 660–666. PubMed

Li T., Jin,Y., Vershon,A.K. and Wolberger,C. (1998) Crystal structure of the MATa1/MATα2 homeodomain heterodimer in complex with DNA containing an A-tract. Nucleic Acids Res., 26, 5707–5718. PubMed PMC

Kim J.L., Nikolov,D.B. and Burley,S.K. (1993) Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature, 365, 520–527. PubMed

Clark K.L., Halay,E.D., Lai,E. and Burley,S.K. (1993) Co-crystal structure of the HNF-3/Fork head DNA-recognition motif resembles histone H5. Nature, 364, 412–420. PubMed

Ghosh G., Vanduyne,G., Ghosh,S. and Sigler,P.B. (1995) Structure of NF-kappa B p50 homodimer bound to a kappa B site. Nature, 373, 303–310. PubMed

Li T., Stark,M.R., Johnson,A.D. and Wolberger,C. (1995) Crystal structure of the MAT 1/MAT alpha 2 homeodomain heterodimer bound to DNA. Science, 270, 262–269. PubMed

Keller W., Konig,P. and Richmond,T.J. (1995) Crystal structure of a bZIP/DNA complex at 2.2 Å: determinants of DNA specific recognition. J. Mol. Biol., 254, 657–667. PubMed

Gewirth D.T. and Sigler,P.B. (1995) The basis for half-site specificity explored through a non-cognate steroid receptor-DNA complex. Nature Struct. Biol., 2, 386–394. PubMed

Hirsch J.A. and Aggarwal,A.K. (1995) Structure of the even-skipped homeodomain complexed to AT-rich DNA: new perspectives on homeodomain specificity. EMBO J., 14, 6280–6291. PubMed PMC

Koenig P., Giraldo,R., Chapman,L. and Rhodes,D. (1996) Crystal structure of the DNA binding domain of yeast RAP1 in complex with a telomeric DNA site. Cell, 85, 125–136. PubMed

Tan S., Hunziker,Y., Sargent,D.F. and Richmond,T.J. (1996) Crystal structure of a yeast TFIIA/TBP/DNA complex. Nature, 381, 127–134. PubMed

Houbaviy H.B., Usheva,A., Shenk,T. and Burley,S.K. (1996) Cocrystal structure of YY1 bound to the adeno-associated virus P5 initiator. Proc. Natl Acad. Sci. USA, 93, 13577–13582. PubMed PMC

Rice P.A., Yang,S.-W., Mizuuchi,K. and Nash,H.A. (1996) Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn. Cell, 87, 1295–1306. PubMed

Tucker-Kellogg L., Rould,M.A., Chambers,K.A., Ades,S.E., Sauer,R.T. and Pabo,C.O. (1997) Engrailed (Gln50→Lys) homeodomain-DNA complex at 1.9 Å resolution: structural basis for enhanced affinity and altered specificity. Structure, 5, 1047–1054. PubMed

Swaminathan K., Flynn,P., Reece,R.J. and Marmorstein,R. (1997) Crystal structure of a Put3-DNA complex reveals a novel mechanism for DNA recognition by a protein containing a Zn2Cys6 binuclear cluster. Nature Struct. Biol., 4, 751–759. PubMed

Muller C.W. and Herrmann,B.G. (1997) Crystallographic structure of the T domain-DNA complex of the brachyury transcription factor. Nature, 389, 884–888. PubMed

Chen X., Ramakrishnan,B., Rao,S.T. and Sundaralingam,M. (1994) Side by side binding of two distamycin a drugs in the minor groove of an alternating B-DNA duplex. Nature Struct. Biol., 1, 169–175. PubMed

Kopka M.L., Goodsell,D.S., Han,G.W., Chiu,T.K., Lown,J.W. and Dickerson,R.E. (1997) Defining GC-specificity in the minor groove: side-by-side binding of the diimidazole. Structure, 5, 1033–1046. PubMed

Quintana J.R., Lipanov,A.A. and Dickerson,R.E. (1991) Low-temperature crystallographic analysis of the binding of the hoechst-33258 to the double-helical DNA dodecamer C-G-C-G-A-A-T-T-C-G-C-G. Biochemistry, 30, 10294–10306. PubMed

Brown D.G., Sanderson,M.R., Garman,E. and Neidle,S. (1992) Crystal structure of a berenil-d(CGCAAATTTGCG) complex. An example of drug-DNA recognition based on sequence-dependent structural features. J. Mol. Biol., 226, 481–490. PubMed

Sriram M., van der Marel,G.A., Roelen,L.P.F., van Boom,J.H. and Wang,A.H.-J. (1992) Conformation of B-DNA containing O6-ethyl G•C base pairs stabilised by minor grove binding drugs: molecular structure of d[CGC(e6G)AATTCGCG] complexed with Hoechst 33258 or Hoechst 33342. EMBO J., 11, 225–232. PubMed PMC

Wood A.A., Nunn,C.M., Czarny,A., Boykin,D.W. and Neidle,S. (1995) Variability in DNA minor groove width recognized by ligand binding: the crystal structure of a bis-benzimidazole compound bound to the DNA duplex d(CGCGAATTCGCG)(2). Nucleic Acids Res., 23, 3678–3684. PubMed PMC

Chen X., Ramakrishnan,B. and Sundaralingam,M. (1997) Crystal structures of the side-by-side binding of distamycin to AT-containing DNA octamers d(ICITACIC) and d(ICATATIC). J. Mol. Biol., 267, 1157–1170. PubMed

Chen X., Ramakrishnan,B. and Sundaralingam,M. (1995) Crystal structures of B-form DNA-RNA chimers complexed with distamycin. Nature Struct. Biol., 2, 733–735. PubMed

Schneider B., Neidle,S. and Berman,H.M. (1997) Conformations of the sugar-phosphate backbone in helical DNA crystal structures. Biopolymers, 42, 113–124. PubMed

Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition

Automatic workflow for the classification of local DNA conformations