Abstract:
:Inducible nitric oxide synthase (iNOS) catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine and O2. In addition to serving as substrate, L-arginine alters the enzyme's heme iron spin equilibrium, increases its NADPH oxidation, and promotes assembly of active dimeric iNOS from inactive monomers. To understand what structural aspects of L-arginine are important for causing these effects, we have studied the interactions of iNOS with several L-arginine and guanidine analogs. Very few analogs supported NO synthesis even when bound to iNOS at saturating or near-saturating levels. In contrast, almost all analogs shifted the heme iron spin equilibrium and either increased or decreased NADPH oxidation by iNOS. The guanidine analogs displayed the same pattern of effects as their amino acid counterparts but exhibited a lower affinity except for analogs containing S-alkylisothiourea or aminoguanidine groups. Most analogs also promoted iNOS dimerization, with hydroxyguanidine and S-ethylisothiourea promoting more dimerization than L-arginine itself. Although the analog concentrations required to promote dimerization of monomers were somewhat higher than those required for binding to dimeric iNOS, they followed the same rank order. The degree of dimerization promoted by each analog did not correlate to its binding affinity, its causing a high- or low-spin shift in heme iron spin state, or to its increasing or decreasing NADPH oxidation. Together, we conclude that the enzyme's high degree of substrate specificity only applies to NO synthesis, in that a number of "inactive" structural analogs still bind to iNOS and affect its heme chemistry and structure in the absence of supporting NO synthesis. These latter affects are mediated through binding of the guanidinium portion of L-arginine and its analogs to a single site within iNOS and are relatively independent of the amino acid portion of the molecule.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Sennequier N,Stuehr DJdoi
10.1021/bi952844esubject
Has Abstractpub_date
1996-05-07 00:00:00pages
5883-92issue
18eissn
0006-2960issn
1520-4995pii
bi952844ejournal_volume
35pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::We have isolated from rabbit liver three cDNA clones of 1400-1800 base pairs that hybridize selectively to RNA from animals treated with phenobarbital. The nucleotide sequences of the cDNAs have been determined. In the protein coding region the nucleotide sequences of two of the cDNAs are 88% homologous, and the third...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00297a005
更新日期:1984-01-17 00:00:00
abstract::Pulsed electron paramagnetic resonance spectroscopy has been used to detect Mn(II)-ligand superhyperfine couplings in complexes with creatine kinase and in the Mn(II) metalloprotein concanavalin A. Electron spin-echo envelopes from Mn(II), bound in these complexes, are modulated by superhyperfine interactions between ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00367a046
更新日期:1986-09-23 00:00:00
abstract::Equilibrium binding experiments are widely used for the accurate characterization of binding and competitive binding behavior in biological systems. Modern high-throughput discovery efforts in chemical biology rely heavily upon this principle. Here, we derive exact analytical expressions for general competitive bindin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048233g
更新日期:2004-12-28 00:00:00
abstract::Channelrhodopsins (ChRs) from green flagellate algae function as light-gated ion channels when expressed heterologously in mammalian cells. Considerable interest has focused on understanding the molecular mechanisms of ChRs to bioengineer their properties for specific optogenetic applications such as elucidating the f...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501243y
更新日期:2015-01-20 00:00:00
abstract::Treatment of ADP-glucose pyrophosphorylase (EC 2.7.7.27) from the cyanobacterium Anabaena PCC 7120 with phenylglyoxal in 50 mM Hepes, pH 8.0, at 25 degrees C resulted in a time- and concentration-dependent loss of enzyme activity. Phosphate, the inhibitor, protected the enzyme from inactivation most effectively, while...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9713355
更新日期:1997-10-21 00:00:00
abstract::Ca2+-induced fusion of phospholipid vesicles (phosphatidylcholine/phosphatidic acid, 9:1 mol/mol) prepared by ethanolic injection was followed by five different procedures: resonance energy transfer, light scattering, electron microscopy, intermixing of aqueous content, and gel filtration through Sepharose 4-B. The fi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00329a015
更新日期:1985-04-09 00:00:00
abstract::Endothelium-derived epoxyeicosatrienoic acids (EETs) relax vascular smooth muscle by activating potassium channels and causing membrane hyperpolarization. Recent evidence suggests that EETs act via a membrane binding site or receptor. To further characterize this binding site or receptor, we synthesized 20-iodo-14,15-...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi102070w
更新日期:2011-05-10 00:00:00
abstract::Extracellular senile plaques composed predominantly of fibrillar amyloid-beta (Abeta) are a major neuropathological feature of Alzheimer's disease (AD). Genetic evidence and in vivo studies suggest that apolipoprotein E (apoE) may contribute to amyloid clearance and/or deposition. In vitro studies demonstrate that nat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0017475
更新日期:2000-12-26 00:00:00
abstract::Oxidation of low-density lipoprotein (LDL), the major cholesterol carrier in plasma, is thought to promote atherogenesis via several mechanisms. One proposed mechanism involves fusion of oxidized LDL in the arterial wall; another involves oxidation-induced amyloid formation by LDL apolipoprotein B. To test these mecha...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700225a
更新日期:2007-05-15 00:00:00
abstract::Mutagenized dockerin domains of endoglucanase CelD (type I) and of the cellulosome-integrating protein CipA (type II) were constructed by swapping residues 10 and 11 of the first or the second duplicated segment between the two polypeptides. These residues have been proposed to determine the specificity of cohesin-doc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011853m
更新日期:2002-02-19 00:00:00
abstract::Clostridial neurotoxins are zinc endopeptidases, and each contains one Zn(2+)/molecule. To investigate the structural/functional role of Zn(2+) in botulinum neurotoxin light chain (the enzymatic subunit of the neurotoxin), the effect of the removal of zinc on protein folding and enzyme kinetics was investigated. The a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0007472
更新日期:2000-08-29 00:00:00
abstract::Lactone-hydrolyzing enzymes derived from some Bacillus species are capable of disrupting quorum sensing in bacteria that use N-acyl-l-homoserine lactones (AHLs) as intercellular signaling molecules. Despite the promise of these quorum-quenching enzymes as therapeutic and anti-biofouling agents, the ring opening mechan...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061238o
更新日期:2006-11-07 00:00:00
abstract::Structurally diverse small molecules, including 5-(2-benzofuryl)-4-phenyl-1,2,4-triazole-3-thiol (BETT), have been identified via high-throughput screening as activators of caspase-3 in HeLa cell extracts. However, little is known about their mechanism of action. In this study, we investigate how BETT regulates prothy...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9022329
更新日期:2010-03-09 00:00:00
abstract::The thermodynamics of the native<-->A state and native<-->unfolded transitions for ubiquitin have been characterized in detail using the denaturants methanol and guanidinium chloride (Gdn.HCl) both separately and in combination. Gdn.HCl destabilizes the partially folded alcohol-induced A state such that the effects of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010767j
更新日期:2001-08-28 00:00:00
abstract::The peptidyl trifluoromethyl ketones Ac-Phe-CF3 (1) and Ac-Leu-Phe-CF3 (2) are inhibitors of chymotrypsin. They differ in Ki (20 and 2 microM, respectively) as well as in their kinetics of association with chymotrypsin in that 1 is rapidly equilibrating, with an association rate too fast to be observed by steady-state...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00485a009
更新日期:1990-08-21 00:00:00
abstract::It is generally accepted that electron transfer in bacterial photosynthesis is driven by the first singlet excited state of a special pair of bacteriochlorophylls (P*). We have examined the first steps of electron transfer in a mutant of the Rhodobacter sphaeroides reaction center in which charge separation from P* is...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9703756
更新日期:1997-06-10 00:00:00
abstract::Peptide-membrane interactions are important for understanding the binding, partitioning, and folding of membrane proteins; the activity of antimicrobial and fusion peptides; and a number of other processes. We describe molecular dynamics simulations (10-25 ns) of two pentapeptides Ace-WLXLL (with X = Arg or Lys side c...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi027001j
更新日期:2003-08-05 00:00:00
abstract::The actin cytoskeleton carries out cellular functions, including division, migration, adhesion, and intracellular transport, that require a variety of actin binding proteins, including myosins. Our focus here is on class II nonmuscle myosin isoforms, NMIIA, NMIIB, and NMIIC, and their regulation by the actin binding p...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi500162z
更新日期:2014-06-24 00:00:00
abstract::The far-ultraviolet circular dichroism spectra of bovine and human prothrombin, prothrombin fragment 1, prethrombin 1, prothrombin fragment 2, and prethrombin 2 (prethrombin 2des(1--13)) were determined and the method of Chen et al. [Chen, Y. H., Yang, J. T., & Martinez, H. M. (1972) Biochemistry 11, 4120--4131; Chen,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00577a017
更新日期:1979-05-15 00:00:00
abstract::Deazapurine-containing secondary metabolites comprise a broad range of structurally diverse nucleoside analogues found throughout biology, including various antibiotics produced by species of Streptomyces bacteria and the hypermodified tRNA bases queuosine and archaeosine. Despite early interest in deazapurines as ant...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900400e
更新日期:2009-05-12 00:00:00
abstract::The dependence of the activity of bovine Cu,Zn superoxide dismutase on pH and ionic strength was extensively investigated in the ranges of pH 7.4-pH 12.3 and of ionic strength of 0.02-0.25 M. The results obtained indicate that two positively charged groups having pK values of approximately 10.1 and 10.8 are involved i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00385a043
更新日期:1987-06-02 00:00:00
abstract::Illuminating Ca2+-depleted photosystem (PS) II membranes generated two new EPR signals at g = 11 and 15 by perpendicular and parallel polarization modes, respectively. Two turnovers of the oxygen evolving center (OEC) beyond the modified S2' state are required for the appearance of these signals. The formation of the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972471c
更新日期:1998-03-03 00:00:00
abstract::While the urea-mediated unfolding pathway of the Escherichia coli aspartate aminotransferase (eAATase) homodimer proceeds through a reversible three-state process with a partially folded dimeric intermediate, D D* 2U (E. Deu and J. F. Kirsch, accompanying paper), that of a cofactor-stabilized form differs. Pyridoxal p...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi602632d
更新日期:2007-05-15 00:00:00
abstract::The RelE and RelB proteins constitute the RNA interferase (toxin) and its cognate inhibitor (antitoxin) components of the Escherichia coli relBE toxin-antitoxin system. Despite the well-described functionality and physiological activity of this system in E. coli, no structural study was performed on the folding and st...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701037e
更新日期:2007-10-30 00:00:00
abstract::The structure of the dimeric form of the protein L7/L12 from ribosomes from Escherichia coli was studied by using the heterobifunctional cross-linker 4-(6-formyl-3-azidophenoxy)butyrimidate. The imidate group of the cross-linker reacts very specifically with Lys-51 of L7/L12. Subsequent cross-linking of this modified ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00507a057
更新日期:1981-02-17 00:00:00
abstract::The crystal structure of the 2[4Fe-4S] ferredoxin from Clostridium acidurici has been solved using X-ray diffraction data extending to atomic resolution, 0.94 A, recorded at 100 K. The model was refined with anisotropic representation of atomic displacement parameters for all non-hydrogen atoms and with hydrogens ridi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972155y
更新日期:1997-12-23 00:00:00
abstract::Biochemical experiments, using the well-defined human liver CYP2C9 expressed in yeast, and molecular modeling techniques were used to derive a predictive model for substrates of CYP2C9. The ability of 10 2-aroylthiophenes related to tienilic acid to act as substrates for CYP2C9 was studied. Four of them were original ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00033a007
更新日期:1995-08-22 00:00:00
abstract::We have examined proteins containing the DNA-binding domain of c-Myb with biophysical methods. This DNA-binding domain consists of three imperfect repeats (R1, R2, and R3) conserved among many species. Our results indicate that the DNA-binding domain forms unspecific and specific complexes with oligodeoxynucleotides. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00252a026
更新日期:1994-12-06 00:00:00
abstract::Raman spectra of the parallel-stranded duplex formed from the deoxyoligonucleotides 5'-d-[(A)10TAATTTTAAATATTT]-3' (D1) and 5'-d[(T)10ATTAAAATTTATAAA]-3' (D2) in H2O and D2O have been acquired. The spectra of the parallel-stranded DNA are then compared to the spectra of the antiparallel double helix formed from the de...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00226a012
更新日期:1991-03-26 00:00:00
abstract::Upon blue light irradiation, photoactive yellow protein (PYP) undergoes a conformational change that involves large movements at the N-terminus of the protein. We reasoned that this conformational change might be used to control other protein or peptide sequences if these were introduced as linkers connecting the N- a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400018h
更新日期:2013-05-14 00:00:00