Abstract:
:Di- and triketone inhibitors of (4-hydroxyphenyl)pyruvate dioxygenase (HPPD) are both effective herbicides and therapeutics. The inhibitory activity is used to halt the production of lipophilic redox cofactors in plants and also in humans to prevent accumulation of toxic metabolic byproducts that arise from specific inborn defects of tyrosine catabolism. The three-dimensional structure of the Fe(II) form of HPPD from Streptomyces avermitilis in complex with the inhibitor 2-[2-nitro-4-(triflouromethyl)benzoyl]-1,3-cyclohexanedione (NTBC) has been determined at a resolution of 2.5 A. NTBC coordinates to the active site metal ion, located at the bottom of a wide solvent-accessible cavity in the C-terminal domain of the protein. The iron is liganded in a predominantly five-coordinate, distorted square-pyramidal arrangement in which Glu349, His187, and His270 are protein-derived ligands and two other ligands are from the 5' and 7' oxygens of NTBC. There is a low-occupancy water molecule in the sixth coordination site in one of the protomers. The distance to His270 is unusually long at 2.5 A, and its orientation is somewhat distorted from ideal ligand geometry to within 2.8 A of the inhibitor nitro group. In contrast to the tetrameric quartenary structure observed for HPPD from other bacterial sources, the asymmetric unit is composed of two weakly associated protomers with a buried surface area of 1266 A(2) and a total of 12 hydrogen-bonding and no electrostatic interactions. The overall tertiary structure is similar to that of HPPD from Pseudomonas fluorescens (Serre et al., (1999) Structure 7, 977-988), although the position of the C-terminal alpha-helix is dramatically shifted. This C-terminal alpha-helix provides Phe364, which in combination with Phe336 sandwiches the phenyl ring of the bound NTBC; no other significant hydrogen-bonding or charge-pairing interactions are observed. Moreover, the structure reveals that, with the exception of Val189, NTBC makes contacts to only fully conserved amino acids. The combination of bidentate metal-ion coordination and pi-stacked aromatic rings is suggestive of a binding mode for the substrate and/or a transition state, which may be the origin of the exceedingly high affinity these inhibitors have for HPPD.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Brownlee JM,Johnson-Winters K,Harrison DH,Moran GRdoi
10.1021/bi049317ssubject
Has Abstractpub_date
2004-06-01 00:00:00pages
6370-7issue
21eissn
0006-2960issn
1520-4995journal_volume
43pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The disulfide structure of sillucin, a highly knotted, cysteine-rich, antimicrobial peptide, isolated from Rhizomucor pusillus, has been determined to be Cys2--Cys7, Cys12--Cys24, Cys13--Cys30, and Cys14--Cys21 by disulfide mass mapping based on partial reduction and CN-induced cleavage enabled by cyanylation. The den...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002229x
更新日期:2001-04-17 00:00:00
abstract::Native EcoRI DNA methyltransferase (Mtase, Mr 38,050) is proteolyzed by trypsin to generate an intermediate 36-kDa fragment (p36) followed by the formation of two polypeptides of Mr 23,000 and 13,000 (p23 and p13, respectively). Protein sequence analysis of the tryptic fragments indicates that p36 results from removal...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00225a030
更新日期:1991-03-19 00:00:00
abstract::The metalloregulatory protein MntR from Bacillus subtilis acts as a transcriptional regulator of manganese homeostasis. MntR is a member of a subfamily of DtxR-related proteins that perform analogous regulatory functions in a variety of pathogenic organisms. Metal ions activate MntR to bind DNA and repress the transcr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0350248
更新日期:2003-11-04 00:00:00
abstract::Ultraviolet resonance Raman (UV RR) spectra are reported for ferricytochrome c from tuna and horse heart at pH 1.6, 7, 10, and 13, representing distinct conformational states of the protein (states II, III, IV, and V, respectively). The spectra were obtained with pulsed laser excitation at 200 and 218 nm, via H2 Raman...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00339a035
更新日期:1985-08-27 00:00:00
abstract::Although the binding of bivalent metal-ion activators to phosphoglucomutase produces substantial changes in the near ultraviolet spectrum of the enzyme, the extent to which aromatic residues are exposed to the aqueous environment, as assessed by means of solvent perturbation spectroscopy (using D2O), does not appear t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00601a031
更新日期:1978-04-18 00:00:00
abstract::Aminoacyl-tRNA synthetases preserve the fidelity of decoding genetic information by accurately joining amino acids to their cognate transfer RNAs. Here, tRNA discrimination at the level of binding by Escherichia coli histidyl-tRNA synthetase is addressed by filter binding, analytical ultracentrifugation, and iodine fo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991182g
更新日期:1999-10-12 00:00:00
abstract::Site-directed mutagenesis, electron microscopy, and X-ray crystallography were used to probe the structural basis of annexin IV-induced membrane aggregation and the inhibition of this property by protein kinase C phosphorylation. Site-directed mutants that either mimic (Thr6Asp, T6D) or prevent (Thr6Ala, T6A) phosphor...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002507s
更新日期:2001-04-03 00:00:00
abstract::Bovine brain adenylate cyclase was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), sodium cholate, sodium deoxycholate, or these detergents plus (NH4)2SO4. The specific activity of the extract obtained with 13 mM CHAPS alone was several times those of the other detergent extracts wi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00258a019
更新日期:1982-07-20 00:00:00
abstract::High-resolution proton nuclear magnetic resonance (1H NMR) measurements were made on myosin, heavy meromyosin (HMM), myosin subfragment 1 (S1), light meromyosin (LMM), and actin. A strong signal from amino acid side chains undergoing motions too fast to be accounted for by simple rotations of groups on a rigid backbon...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00586a031
更新日期:1979-09-18 00:00:00
abstract::Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, named protein B1 (170 000) and protein B2 (87 000). We purified and characterized five monoclonal antibodies against B1 and three against B2 from hybridomas obtained by fusion of spleen cells from immunized mice and the myeloma cell ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00352a018
更新日期:1986-02-25 00:00:00
abstract::Here we demonstrate that monovalent cations can localize around B-DNA in geometrically regular, sequence-specific sites in oligonucleotide crystals. Positions of monovalent ions were determined from high-resolution X-ray diffraction of DNA crystals grown in the presence of thallium(I) cations (Tl(+)). Tl(+) has previo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010391+
更新日期:2001-08-28 00:00:00
abstract::Histone H10 differs substantially from H1 in a 37-residue region of the primary structure that is conserved between the usual H1 histones of fish and mammals. Instead, H10 is homologous to H5 in this region. Histones H10 and H5 might be classified together in a histone category distinct from the usual H1. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00511a035
更新日期:1981-04-14 00:00:00
abstract::An attractive strategy for the development of anti-retroviral drugs is the exploration of compounds that mimic RNA control regions of the viral genome and act as "decoys" to sequester viral gene regulatory proteins. Decoys consisting of RNA, however, are chemically unstable and readily degraded by cellular nucleases. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi961980w
更新日期:1997-01-21 00:00:00
abstract::In contrast to all other known pyrophosphatases, Moorella thermoacetica pyrophosphatase (mtCBS-PPase) contains nucleotide-binding CBS domains and is thus strongly regulated by adenine nucleotides. Stopped-flow measurements using a fluorescent AMP analogue, 2'(3')-O-(N-methylanthranoyl)-AMP (Mant-AMP), reveal that nucl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9019737
更新日期:2010-02-09 00:00:00
abstract::There is no complete understanding of how serine protease inhibitors of the serpin family inhibit their target enzymes. Structural and biochemical studies have suggested that serpins utilize a mechanism that is distinct from the standard mechanism of inhibition proposed for most small protein protease inhibitors. Prot...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960233w
更新日期:1996-06-11 00:00:00
abstract::Marijuana is the most widely abused illegal drug, and its spectrum of effects suggests that several receptors are responsible for the activity. Two cannabinoid receptor subtypes, CB1 and CB2, have been identified, but the complex pharmacological properties of exogenous cannabinoids and endocannabinoids are not fully e...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200010k
更新日期:2011-06-28 00:00:00
abstract::Intact rat liver mitochondria were treated with compounds derived from the reaction of fluorescamine with various types of primary amines, including the mycosamine-containing antibiotics amphotericin B and nystatin. The effect of varying amounts of these compounds on ATPase-linked inorganic phosphate (Pi) formation on...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00550a031
更新日期:1980-04-29 00:00:00
abstract::Human plasma phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs). We determined phospholipid transfer activity and HDL binding ability in wild-type PLTP and in 16 PLTP variants created by replacing 12 charged amino acids by site-directed mutag...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi027006g
更新日期:2003-04-22 00:00:00
abstract::The reaction of ferric cytochrome c peroxidase (CcP) from Saccharomyces cerevisiae with peroxide produces compound I, characterized by both an oxyferryl iron center and a protein-based free radical. The electron paramagnetic resonance (EPR) signal of the CcP compound I radical can be resolved into a broad majority com...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00221a036
更新日期:1991-02-19 00:00:00
abstract::Unoccupied estrogen receptor (ER) can be extracted from tissues by homogenization with a hypotonic buffer, whereas hormone-occupied ER becomes tightly bound to the nuclear pellet and must be extracted with high-salt-containing buffers. The molecular basis for estrogen-induced tight nuclear binding of ER remains an imp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi982190k
更新日期:1999-06-01 00:00:00
abstract::Based on the atomic structures of the mitochondrial cytochrome bc(1) complex, it has been proposed that the soluble domain of the [2Fe-2S] Rieske iron-sulfur protein (ISP) must rotate by ca. 60 degrees and translate through an appreciable distance between two binding sites, proximal to cytochrome c(1) and to the lumen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9921992
更新日期:2000-03-14 00:00:00
abstract::The abnormal isoform of the scrapie prion protein PrPSc is both a host-derived protein and a component of the infectious agent causing scrapie. PrPSc and the normal cellular isoform PrPC have different physical properties that apparently arise from a posttranslational event. Both PrP isoforms are covalently modified a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00474a028
更新日期:1990-06-05 00:00:00
abstract::Triglyceride analogues were synthesized in which one of the primary acyl ester functions has been replaced by an alkyl group and the secondary acyl ester bond has been replaced by an acyl amino bond. The chain length at either position was varied, and both (R)- and (S)-enantiomers of each compound were synthesized. Th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00019a020
更新日期:1995-05-16 00:00:00
abstract::Sequential 1H NMR assignments of a metallothionein from Neurospora crassa have been accomplished by the combined use of COSY, 2QF-COSY, HOHAHA, and rotating-frame NOE experiments. All potentially observable resonances were assigned except for the epsilon-NH3 group of the C-terminal lysine. 1H NOEs, when observed in th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00433a038
更新日期:1989-04-04 00:00:00
abstract::The ability to undergo large-scale domain rearrangements is essential for the substrate-binding function of periplasmic binding proteins (PBPs), which are indispensable for nutrient uptake in Gram-negative bacteria. Crystal structures indicate that PBPs typically adopt either an "open" unliganded configuration or a "c...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi902045p
更新日期:2010-03-09 00:00:00
abstract::Anaerobic induction of light harvesting and reaction center gene expression involves two transacting factors termed RegA and RegB. Sequence and mutational analysis has indicated that RegA and RegB constitute cognate components of a prokaryotic sensory transduction cascade with RegB comprising a membrane-spanning senso...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00002a002
更新日期:1995-01-17 00:00:00
abstract::Microtubules, ordinarily cold-labile structures, are made entirely resistant to cold temperature by the presence of substoichiometric amounts of STOP (stable tubule only polypeptide), a microtubule-associated protein. We have produced a monoclonal antibody which specifically recognizes a 145-kDa protein previously imp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00428a064
更新日期:1989-01-24 00:00:00
abstract::To be fully active and participate in the metabolism of phosphorylated nucleotides, most nucleoside diphosphate kinases (NDPKs) have to assemble into stable hexamers. Here we studied the role played by six intersubunit salt bridges R80-D93 in the stability of NDPK from the pathogen Mycobacterium tuberculosis ( Mt). Mu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b01308
更新日期:2019-03-12 00:00:00
abstract::Kinetic analysis and modeling studies of HIV-1 and HIV-2 proteinases were carried out using the oligopeptide substrate [formula: see text] and its analogs containing single amino acid substitutions in P3-P3' positions. The two proteinases acted similarly on the substrates except those having certain hydrophobic amino ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00135a008
更新日期:1992-05-26 00:00:00
abstract::The ATP-hydrolyzing portion of the proton pump from clathrin-coated vesicles (isolated from calf brain) was solubilized with three nondenaturing detergents (cholate, octyl glucoside, and Triton X-100). The hydrodynamic properties of the solubilized (Mg2+)-ATPase were then determined by sedimentation analysis in H2O an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00363a015
更新日期:1986-07-29 00:00:00