Abstract:
:The X-ray crystal structure of the complex of the B-DNA dodecamer CGCGAATTCGCG with the antitumor drug netropsin has been reexamined to locate the drug accurately for computer-based drug design. The optimum solution is with the drug centered in the AATT region of the minor groove, making three good bifurcated hydrogen bonds with adenine N3 and thymine O2 atoms along the floor of the groove. Pyrrole rings of netropsin are packed against the C2 positions of adenines, leaving no room for the amine group of guanine and, hence, providing a structural rationale for the A.T specificity of netropsin. An alternative positioning in which the drug is shifted along the minor groove by ca. one-half base pair step is rejected on the basis of free R factor calculations and the appearance of the original drug-free difference maps. Final omit maps, although of more pleasing appearance, are not a dependable means of discriminating between right and wrong structures. The shifted alternative drug position ignores potential hydrogen bonding along the floor of the groove, provides no explanation for netropsin's observed A.T specificity, and is contradicted by NMR results [Patel, D. J. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 6424].
journal_name
Biochemistryjournal_title
Biochemistryauthors
Goodsell DS,Kopka ML,Dickerson REdoi
10.1021/bi00015a009subject
Has Abstractpub_date
1995-04-18 00:00:00pages
4983-93issue
15eissn
0006-2960issn
1520-4995journal_volume
34pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::5-HT(2A) serotonin receptors represent the principal molecular targets for LSD-like hallucinogens and atypical antipsychotic drugs. It has been proposed that a dysregulation of 5-HT(2A) receptor-mediated signaling may contribute to the pathogenesis of schizophrenia and related diseases. A major mechanism for the atten...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035061z
更新日期:2003-09-16 00:00:00
abstract::Crystallographic studies have demonstrated two flavin conformations for p-hydroxybenzoate hydroxylase (PHBH) [Gatti, D. L., Palfey, B. A. , Lah, M. S., Entsch, B., Massey, V., Ballou, D. P., & Ludwig, M. L. (1994) Science 266, 110-114. Schreuder, H. A., Mattevi, A., Obmolova, G., Kalk, K. H., Hol, W. G. J., van der Bo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971427u
更新日期:1997-12-16 00:00:00
abstract::Oligonucleotide-directed triple helix formation provides an elegant rational basis for gene-specific DNA targeting and has been widely used to interfere with gene expression ("antigene" strategies) and as a molecular tool for biological studies. Various strategies have been developed to introduce sequence modification...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi001605a
更新日期:2001-02-13 00:00:00
abstract::The trans-aconitate methyltransferase from the bacterium Escherichia coli catalyzes the monomethyl esterification of trans-aconitate and related compounds. Using two-dimensional (1)H/(13)C nuclear magnetic resonance spectroscopy, we show that the methylation is specific to one of the three carboxyl groups and further ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0022902
更新日期:2001-02-20 00:00:00
abstract::Escherichia coli DNA photolyase contains a stable flavin radical and a second chromophore (SC) of unknown structure. The effects of flash (both conventional and laser) excitation of either the radical alone or both the radical and the second chromophore have been investigated by variation of the excitation wavelengths...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00389a007
更新日期:1987-07-28 00:00:00
abstract::Steroidogenic acute regulatory protein (StAR) rapidly stimulates the movement of cholesterol into adrenal and gonadal mitochondria to mediate the acute steroidogenic response; StAR mutations cause potentially lethal congenital lipoid adrenal hyperplasia (lipoid CAH). Bacterially expressed wild-type StAR and four amino...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980588a
更新日期:1998-07-07 00:00:00
abstract::Oligodeoxyribonucleotides cross-linked by reductively activated mitomycin C (MC) were prepared and purified for the first time. The cross-linked products were structurally characterized by nucleoside and MC-nucleoside adduct analysis. Optimal conditions were established for the cross-linking reaction, resulting in hig...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00464a015
更新日期:1990-03-27 00:00:00
abstract::The reaction of cytochrome c oxidase with dioxygen has been studied by means of time-resolved measurements of electrical membrane potential (DeltaPsi). Microsecond time resolution was achieved by starting with the CO-inhibited enzyme, which was photolyzed after addition of oxygen. The time course of the reaction could...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982275l
更新日期:1999-03-02 00:00:00
abstract::Heme oxygenases convert heme to free iron, CO, and biliverdin. Saccharomyces cerevisiae and Candida albicans express putative heme oxygenases that are required for the acquisition of iron from heme, a critical process for fungal survival and virulence. The putative heme oxygenases Hmx1 and CaHmx1 from S. cerevisiae an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061429r
更新日期:2006-12-12 00:00:00
abstract::Zinc, the catalytically essential metal of angiotensin converting enzyme (ACE), has been replaced by cobalt(II) to give an active, chromophoric enzyme that is spectroscopically responsive to inhibitor binding. Visible absorption spectroscopy and magnetic circular dichroic spectropolarimetry have been used to character...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00397a014
更新日期:1987-11-17 00:00:00
abstract::Acyl carrier protein (ACP) is a cofactor in a variety of biosynthetic pathways, including fatty acid metabolism. Thus, it is of interest to determine structures of physiologically relevant ACP-fatty acid complexes. We report here the NMR solution structures of spinach ACP with decanoate (10:0-ACP) and stearate (18:0-A...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi052062d
更新日期:2006-04-25 00:00:00
abstract::Protein splicing is a self-catalyzed post-translational modification in which the intein enzyme excises itself from a precursor protein and ligates the flanking sequences to produce a mature protein. We report the solution structure of a 136-residue DnaX mini-intein enzyme derived from the cyanobacterium Spirulina pla...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.0c00828
更新日期:2020-12-22 00:00:00
abstract::The active site structures of human Q31 granzyme A, murine granzymes (A, B, C, D, E, and F), and human granzymes (A, B, and 3) isolated from cytotoxic T lymphocytes (CTL) were studied with peptide thioester substrates, peptide chloromethyl ketone, and isocoumarin inhibitors. Human Q31, murine, and human granzyme A hyd...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00222a027
更新日期:1991-02-26 00:00:00
abstract::We measure the effects of low concentrations of helix-stabilizing cosolvents, including 2,2,2-trifluoroethanol (TFE), on the thermodynamics and kinetics of folding of the dimeric alpha-helical coiled coil derived from the leucine zipper region of bZIP transcriptional activator GCN4. The change in kinetic behavior upon...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981641y
更新日期:1998-10-13 00:00:00
abstract::We report here that the DNA strand scission by dynemicin A is not only sequence-specific but also conformation-specific. The salt-induced B----Z conformational transition dramatically enhanced the cleavage by dynemicin A in a B-Z junction region. By contrast, the bleomycin-Fe(II) complex, the elsamicin A-Fe(II) comple...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00144a019
更新日期:1992-07-28 00:00:00
abstract::The first indication of the size of a conformational change implicated in ion transport by sodium pump has been obtained by measuring the change in efficiency of fluorescence energy transfer between two specific locations on the alpha-subunit. The donor (5'-(iodoacetamido)fluorescein) attaches covalently to cysteine-4...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960407+
更新日期:1996-06-25 00:00:00
abstract::The anaerobic global regulator FNR from Escherichia coli is a [4Fe-4S](2+) cluster-containing dimer that is inactivated by O(2) through disruption of the Fe-S cluster and conversion to the monomeric apoprotein. It was shown that apo-FNR is subject to ClpXP proteolysis, and two recognition sites, amino acids 5-11 and a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi2018688
更新日期:2012-06-26 00:00:00
abstract::The interaction of bovine spleen profilin with ATP- and ADP-G-actin and poly(L-proline) has been studied by spectrofluorimetry, analytical ultracentrifugation, and rapid kinetics in low ionic strength buffer. Profilin binding to G-actin is accompanied by a large quenching of tryptophan fluorescence, allowing the measu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00194a011
更新日期:1994-07-19 00:00:00
abstract::CDPKs are a family of calcium (Ca2+)-dependent protein kinases which are defined by a carboxyl-terminal calmodulin-like domain. Mutational analysis indicates that the junction domain, which joins the kinase and calmodulin-like domains, contains an autoinhibitor. CDPK isoform AK1 from Arabidopsis was expressed in Esche...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00189a031
更新日期:1994-06-14 00:00:00
abstract::Neutrophil elastase (NE), a mediator of inflammation, binds with high affinity numerous anionic molecules including suramin, a polysulfated naphthylurea, which inhibits it with a Ki of 0.2 microM and a 4:1 suramin:NE stoichiometry and thus constitutes a potential therapeutic agent. In an attempt to locate the suramin ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971029r
更新日期:1997-12-16 00:00:00
abstract::The water-oxidizing complex of photosystem II cycles through five oxidation states, denoted S(i)() (i = 0-4), during water oxidation to molecular oxygen, which appears at the (transient) S(4) state. The recent detection of bimodal EPR signals from the S(3) state [Matsukawa, T., Mino, H., Yoneda, D., Kawamori, A. (1999...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0159938
更新日期:2002-07-30 00:00:00
abstract::The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis of an aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assembly of the antibiotics' polyketide backbone. The terminal enzyme of AHBA formation, AHBA synthase, is a dimeric, pyridoxal 5'-pho...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi990018q
更新日期:1999-08-03 00:00:00
abstract::Structural changes in the complex formation between transducin and metarhodopsin II, the activated form of photolyzed rhodopsin, in visual transduction processes were analyzed by Fourier transform infrared spectroscopy. The spectrum of the complex was obtained by subtracting the contribution of metarhodopsin I and unc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960911e
更新日期:1996-10-15 00:00:00
abstract::The side chains of the interacting pair Asp237(helix VII)-Lys358(helix XI) or Asp240(helix VII)-Lys319(helix X) in the lactose permease of Escherichia coli were extended by replacement with Glu and/or Arg or by site-specific derivatization of single-Cys replacement mutants. Iodoacetic acid was used to carboxymethylate...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00089a019
更新日期:1993-09-28 00:00:00
abstract::Thymidylate synthase from phage T4 (T4TS) is part of a complex of several enzymes required for coordinate DNA synthesis in infected Escherichia coli cells. It has been proposed that similar complexes of enzymes related to DNA synthesis are also functional in eukaryotes [Pardee, A. B. (1989) Science 246, 603-608]. To d...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00255a028
更新日期:1994-12-27 00:00:00
abstract::Homoserine transacetylase catalyzes one of the required steps in the biosynthesis of methionine in fungi and several bacteria. We have determined the crystal structure of homoserine transacetylase from Haemophilus influenzae to a resolution of 1.65 A. The structure identifies this enzyme to be a member of the alpha/be...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051951y
更新日期:2005-12-06 00:00:00
abstract::NMR spectroscopic experiments were performed to study the structure of synthetic peptides identical to two extracellular regions of the human thrombin receptor. The smaller molecule, comprising 14 amino acids, was biologically active and was equivalent to the "tethered ligand" exposed after cleavage of the receptor by...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00186a005
更新日期:1994-05-24 00:00:00
abstract::The temperature-composition phase diagram of mixed dimyristoylphosphatidylserine (DMPS) and dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles was determined in the presence and absence of bound bovine prothrombin by monitoring the phospholipid order-disorder phase separation using diphenylhexatriene (DP...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00480a023
更新日期:1990-07-17 00:00:00
abstract::The Ca2+-dependent, reversible, interaction of cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase with its activator has been used to purify the enzyme by affinity chromatography. Activator-dependent cAMP phosphodiesterase is only a minor component of the proteins specifically adsorbed in the presence of Ca...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00594a017
更新日期:1978-01-10 00:00:00
abstract::The photocycle of the blue-light photoreceptor protein Photoactive Yellow Protein (PYP) was studied at reduced relative humidity (RH). Photocycle kinetics and spectra were measured in thin films of PYP in which the relative humidity was set at values between 29 and 98% RH with saturated solutions of various salts. We ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi050237d
更新日期:2005-06-28 00:00:00