Abstract:
:Flavohemoglobins (flavoHbs) are enzymes that operate primarily as nitric oxide dioxygenases and shuttle thereby electrons among NAD(P)H, FAD, heme, and a ligated redox-active substrate such as O(2). They function in the bacterial defense against nitrosative stress and are therefore considered as targets for new antibiotic drugs. Recently, azole derivatives were proven to be attractive nitric oxide dioxygenase inhibitors, and to explore their binding characteristics, we determined the X-ray structure of the flavoHb from Ralstonia eutropha in a complex with miconazole (FHP(M)), econazole (FHP(E)), and ketoconazole (FHP(K)). In agreement with UV-vis spectroscopic data, one azole compound binds inside the distal heme pocket and ligates to the heme iron by its imidazole substituent. The two additional substituents, mostly chlorinated phenyl groups, form a series of van der Waals contacts with the protein matrix. Both interactions explain their high affinity for flavoHbs, the binding constants being 2.6, 1.2, and 11.6 μM for miconazole, econazole, and ketoconazole, respectively. The FHP(M) and FHP(Lip) (flavoHbs originally loaded with a phospholipid) structures share an "open" state and the FHP(E) and FHP(K) structures a "closed" state. Although the azole compounds were able to push the lipid out of its binding site, a fatty acid fragment is still bound inside the heme pocket of FHP(E) and FHP(K) and dictates the state of the protein. The ligand-induced open-to-closed transition involves a reorientation of the NADH domain accompanied by conformational changes in the C-terminal arm, helix E, and the CE loop resulting in an encapsulation of the heme-binding pocket. Implications of the observed open-to-closed process on the catalytic cycle are discussed.
journal_name
Biochemistryjournal_title
Biochemistryauthors
El Hammi E,Warkentin E,Demmer U,Limam F,Marzouki NM,Ermler U,Baciou Ldoi
10.1021/bi101650qsubject
Has Abstractpub_date
2011-02-22 00:00:00pages
1255-64issue
7eissn
0006-2960issn
1520-4995journal_volume
50pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Hirudin is the most potent and specific thrombin inhibitor from medicinal leech with a Ki value of 2.2 x 10(-14) M. It consists of an active site inhibitor segment, hirudin1-48, a fibrinogen-recognition exosite inhibitor segment, hirudin55-65, and a linker, hirudin49-54, connecting these inhibitor segments. The role o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00027a021
更新日期:1995-07-11 00:00:00
abstract::Enzyme divergence within three species of the genus Photobacterium (P. fischeri, P. leiognathi, and P. phosphoreum) was studied by comparing the catalytic characteristics and quaternary interactions of bacterial luciferases isolated from each species. Each luciferase was composed of two subunits of different molecular...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00563a009
更新日期:1980-10-28 00:00:00
abstract::The 2.15 A resolution crystal structure of arginase from Plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) (K(d) = 11 microM). This is the first crystal structure of a parasitic arginase. Various protein const...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100390z
更新日期:2010-07-06 00:00:00
abstract::The mammalian plasma vitamin D binding protein (DBP), or Gc-globulin, is recognized to have at least two functional properties: sterol binding and G-actin sequestration. Affinity labeling of the sterol binding site with the radioactive electrophilic ligand, 3 beta-(bromoacetoxy)-25-hydroxycholecalciferol, followed by ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00146a021
更新日期:1992-08-11 00:00:00
abstract::Oxygen binding curves of sol-gel-encapsulated deoxy human adult hemoglobin (HbA) have previously revealed two distinct noncooperative populations with oxygen binding affinities approximately 1000 and 100 times lower than that of the high-affinity R state. The two populations which have been termed the low-affinity (LA...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048531d
更新日期:2004-11-02 00:00:00
abstract::The (+)-trans-anti-benzo[a]pyrene adduct formed at the N2 amino group of guanine is the major adduct found after metabolic activation of the ubiquitous carcinogen benzo[a]pyrene. The carcinogenic and mutagenic properties of the (+)-trans-anti-BP adduct, as well as related adducts, have been extensively studied. A DNA ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00010a004
更新日期:1995-03-14 00:00:00
abstract::The light-driven enzyme NADPH:protochlorophyllide oxidoreductase (POR) catalyzes the reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide), a key regulatory step in the chlorophyll biosynthesis pathway. As POR is light activated, it allows intermediates in the reaction pathway to be observed by initiat...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0268448
更新日期:2003-01-21 00:00:00
abstract::The bacterial photosynthetic reaction center is the evolutionary ancestor of the Photosystem II reaction center. These proteins share the same fold and perform the same biological function. Nevertheless, the details of their molecular reaction mechanism differ. It is of significant biological and biochemical interest ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi802033k
更新日期:2009-02-17 00:00:00
abstract::The reaction center protein D1 in photosystem II shows a high turnover during illumination. The degradation of the D1 protein is preceded by photoinhibition of the electron transport in photosystem II. There are two distinct mechanisms for this: acceptor-side- and donor-side-induced photoinhibition. Here, donor-side-i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960083p
更新日期:1996-06-18 00:00:00
abstract::Nine monoclonal antibodies were used to test calcium and EDTA effects on the molecular conformation of ventricular VLC2 within myosin. Antibody epitopes were located in six domains of VLC2 using recombinant proteins. The apparent association constants of these antibodies were measured in solution in the presence of ca...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00208a005
更新日期:1994-10-25 00:00:00
abstract::Site-directed mutagenesis and random mutagenesis were used to produce variants of subtilisin BPN' (Bacillus amyloliquefaciens) protease with variable surface adsorption properties. Protease adsorption and peptide hydrolysis rate were measured for these variants using a model substrate consisting of a peptide covalentl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi951990h
更新日期:1996-03-12 00:00:00
abstract::The substrate profiles for three uncharacterized enzymes (YcjM, YcjT, and YcjU) that are expressed from a cluster of 12 genes ( ycjM-W and ompG) of unknown function in Escherichia coli K-12 were determined. Through a comprehensive bioinformatic and steady-state kinetic analysis, the catalytic function of YcjT was dete...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00392
更新日期:2018-05-15 00:00:00
abstract::The mechanism of binding of reduced 1-(2-carboxyphenylamino)-1-deoxyribulose 5-phosphate (rCdRP) to two different binding sites on the bifunctional enzyme is determined by kinetic studies, using temperature-jump and stopped-flow equipment with fluorescence detection. Two rapid binding processes and a comparatively slo...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00593a030
更新日期:1979-12-25 00:00:00
abstract::Light-harvesting complex II (LHC-II) regulates the light energy distribution between photosystem I and II in plants. This process is mediated by phosphorylation of the LHC-II protein, which depends on the oxidation state of photosynthetic electron carriers. In addition to this regulatory mechanism, it has recently bee...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034114+
更新日期:2003-09-02 00:00:00
abstract::The role of acetylation on the conformation and association state of the inner core histone octamer isolated from HeLa cells was examined. Preparation of suitable quantities of pure acetylated and control inner core histones from HeLa cells required the development of a new preparative procedure. The results from size...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00384a041
更新日期:1987-05-19 00:00:00
abstract::Temperature-jump experiments were performed with di-, tetra-, and hexasaccharides derived from type III pneumococcal polysaccharide using a homogeneous corresponding antibody IgG 45-394. A decrease in stability of the oligosaccharide-antibody complexes with decreasing chain length was observed and entirely reflected i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00637a023
更新日期:1977-09-06 00:00:00
abstract::The plasma membrane of the Ehrlich ascites tumor cell contains an NADH dehydrogenase. This activity was shown not to be due to contamination by other subcellular membranes. A variety of electron acceptors have been compared as to rate with the following result: ferricyanide greater than cytochrome c greater than cytoc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00575a021
更新日期:1979-04-17 00:00:00
abstract::Here, we biochemically characterize Dictyostelium myosin II mutants that were previously phenotypically selected following random mutagenesis and shown to lie in the actin binding domain [Patterson, B., & Spudich, J. A. (1996) Genetics 143, 801-810]. We show that the conditional loss of myosin-dependent activity in vi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi963141f
更新日期:1997-07-15 00:00:00
abstract::A soluble Ca2+/calmodulin-dependent protein kinase has been purified from rat brain to near homogeneity by using casein as substrate. The enzyme was purified by using hydroxylapatite adsorption chromatography, phosphocellulose ion-exchange chromatography, Sepharose 6B gel filtration, affinity chromatography using calm...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00318a018
更新日期:1984-11-06 00:00:00
abstract::All-trans-retinol is the precursor for all-trans-retinoic acid, the activating ligand for nuclear transcription factors retinoic acid receptors. In the cytosol of various cells, most retinol exists in a bound form, complexed with cellular retinol binding protein type I (holo-CRBP). Whether retinoic acid is produced fr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026836r
更新日期:2003-01-28 00:00:00
abstract::Two dioxygenases (ARD and ARD') were cloned from Klebsiella pneumoniae that catalyze different oxidative decomposition reactions of an advanced aci-reductone intermediate, CH(3)SCH(2)CH(2)COCH(OH)=CH(OH) (I), in the methionine salvage pathway. The two enzymes are remarkable in that they have the same polypeptide seque...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010110y
更新日期:2001-05-29 00:00:00
abstract::An empirical preduction algorithm which uses information on the shrs on either side) interactions in 20 proteins to assign every residue in a protein to one of five conformational states is described. The conformational states are defined in terms of the backbone dihedral angles of the residue so that the prediction a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00668a030
更新日期:1976-11-16 00:00:00
abstract::Ionizing radiation, free radicals, and reactive oxygen species produce hundreds of different DNA lesions. Clustered lesions are typical for ionizing radiation. They compromise the efficiency of the base excision repair (BER) pathway, and as a consequence, they are much more toxic and mutagenic than isolated lesions. D...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00396
更新日期:2016-07-19 00:00:00
abstract::The substrate-bound form of the enzyme heme oxygenase (HO), which catalyzed the stereospecific alpha-meso bridge cleavage of hemin to yield biliverdin IX alpha, has been investigated by 1H NMR in both its primarily high-spin and its cyanide-inhibited low-spin forms. Both derivatives yield 1H NMR spectra indicative of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00187a033
更新日期:1994-05-31 00:00:00
abstract::The operations within a living cell depend on the collective activity of networks of proteins, sometimes termed "interactomes". Within these networks, most proteins interact with few partners, while a small proportion of proteins, called hubs, participate in a large number of interactions and play a central role in or...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi701995m
更新日期:2008-01-15 00:00:00
abstract::NMR spectroscopy has been used to study the interaction of aminoglycoside antibiotics with an aminoglycoside antibiotic 3'-phosphotransferase [APH(3')-IIIa]. APH(3')-IIIa is an enterococcal enzyme that is responsible for the ATP-dependent O-phosphorylation of a broad range of aminoglycoside antibiotics. The NMR method...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9626822
更新日期:1997-03-04 00:00:00
abstract::By use of six highly purified exoglycosidases with well-defined specificity, the oligosaccharide units of human plasma beta 2-glycoprotein I (beta 2I) were modified by sequential enzymatic degradation. The released monosaccharides (NeuAc, Gal, GlcNAc, and Man) were quantified, and the carbohydrate compositions of the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00478a020
更新日期:1990-07-03 00:00:00
abstract::The Mn4 complex which is involved in water oxidation in photosystem II (PSII) is known to exhibit two types of EPR signals in the S2 state, one of the five redox states of the enzyme cycle: either a multiline signal (S = 1/2) or a signal at g = 4.1 (S = 3/2 or S= 5/2). The S = 1/2 state can be converted to that respon...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9728710
更新日期:1998-03-24 00:00:00
abstract::Lipid-protein interactions in bovine rod outer segment disk membranes have been studied by using a series of eight stearic acid spin-label probes which were labeled at different carbon atom positions in the chain. In randomly oriented membrane dispersions, the electron spin resonance (ESR) spectra of the C-8, C-9, C-1...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00375a005
更新日期:1987-01-13 00:00:00
abstract::Synaptotagmin I is the calcium sensor in synchronous neurotransmitter release caused by fusion of synaptic vesicles with the presynaptic membrane in neurons. Synaptotagmin I interacts with acidic phospholipids, but also with soluble N-ethylmaleimide-sensitive factor attachment receptors (SNAREs), at various stages in ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101864k
更新日期:2011-04-05 00:00:00