Abstract：
:Macrophage migration inhibitory factor (MIF) is a pro-inflammatory and tumor-promoting cytokine that occurs in two redox-dependent immunologically distinct conformational isoforms. The disease-related structural isoform of MIF (oxMIF) can be specifically and predominantly detected in the circulation of patients with inflammatory diseases and in tumor tissue, whereas the ubiquitously expressed isoform of MIF (redMIF) is abundantly expressed in healthy and diseased subjects. In this article, we report that cysteine 81 within MIF serves as a "switch cysteine" for the conversion of redMIF to oxMIF. Modulating cysteine 81 by thiol reactive agents leads to significant structural rearrangements of the protein, resulting in a decreased β-sheet content and an increased random coil content, but maintaining the trimeric quaternary structure. This conformational change in the MIF molecule enables binding of oxMIF-specific antibodies BaxB01 and BaxM159, which showed beneficial activity in animal models of inflammation and cancer. Crystal structure analysis of the MIF-derived EPCALCS peptide, bound in its oxMIF-like conformation by the Fab fragment of BaxB01, revealed that this peptide adopts a curved conformation, making the central thiol protein oxidoreductase motif competent to undergo disulfide shuffling. We conclude that redMIF might reflect a latent zymogenic form of MIF, and formation of oxMIF leads to a physiologically relevant, i.e., enzymatically active, state.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Schinagl A,Kerschbaumer RJ,Sabarth N,Douillard P,Scholz P,Voelkel D,Hollerweger JC,Goettig P,Brandstetter H,Scheiflinger F,Thiele Mdoi
10.1021/acs.biochem.7b01156subject
Has Abstractpub_date
2018-03-06 00:00:00pages
1523-1532issue
9eissn
0006-2960issn
1520-4995journal_volume
57pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:The heme-regulated inhibitor (HRI) of protein synthesis becomes activated in rabbit reticulocyte lysates in response to a variety of conditions including heme-deficiency, addition of oxidants, and heat shock. Activated HRI inhibits translation by catalyzing the phosphorylation of the alpha-subunit of eukaryotic initia...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00080a001
更新日期：1993-07-27 00:00:00
abstract：:14C-Labeled fluorodinitrobenzene and N-ethylmaleimide have been used as chemical probes of the conformational states of myosin induced by the binding of MgADP and MgATP. The results indicate that in the high-energy conformation, MMgADP-Pi, the essential thiols are protected from modification but their diminished react...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00643a005
更新日期：1977-11-29 00:00:00
abstract：:(Z)-3-(Fluoromethyl)phosphoenolpyruvate has been synthesized in nine chemical steps from glyoxylic acid. The compound is stable at pH 3, but at pH 8 it decomposes within seconds to give 2-oxo-3-butenoate. When 3-(fluoromethyl)phosphoenolpyruvate is added to a solution of phosphoenolpyruvate carboxylase or pyruvate kin...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00404a039
更新日期：1988-02-23 00:00:00
abstract：:Catalase HPII from Escherichia coli is a homotetramer of 753 residue subunits. The multimer displays a number of unusual structural features, including interwoven subunits and a covalent bond between Tyr415 and His392, that would contribute to its rigidity and stability. As the temperature of a solution of HPII in 50 ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi982863z
更新日期：1999-03-30 00:00:00
abstract：:(S)-Mandelate dehydrogenase from Pseudomonas putida belongs to a FMN-dependent enzyme family that oxidizes (S)-alpha-hydroxyacids. Despite a high degree of sequence and structural similarity, this family can be divided into three subgroups based on the different oxidants utilized in the second oxidative half-reaction....
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi049005p
更新日期：2004-08-24 00:00:00
abstract：:Oligonucleotides capable of sequence-specific triple helix formation have been proposed as DNA binding ligands useful for modulation of gene expression and for directed genome modification. However, the effectiveness of such triplex-forming oligonucleotides (TFOs) depends on their ability to bind to their target sites...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi982290q
更新日期：1999-02-09 00:00:00
abstract：:The functional interaction of the recombinant alpha 2 adrenergic receptor subtypes, alpha 2-C10 (the human platelet alpha 2 receptor, equivalent to the alpha 2 A subtype) and alpha 2-C4 (an alpha 2 receptor subtype cloned from a human kidney cDNA library), with G proteins was characterized in an in vitro reconstitutio...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00227a024
更新日期：1991-04-02 00:00:00
abstract：:Adenylosuccinate synthetase catalyzes the first committed step in the de novo biosynthesis of AMP, coupling L-aspartate and IMP to form adenylosuccinate. Km values of IMP and 2'-deoxy-IMP are nearly identical with each substrate supporting comparable maximal velocities. Nonetheless, the Km value for L-aspartate and th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0607498
更新日期：2006-09-26 00:00:00
abstract：:A generalized set of fluorescence polarization intensities and electron paramagnetic resonance (EPR) spectra from multiple fluorescent and EPR probes of a specific site on an oriented and immobilized protein element in a biological assembly, combined with anisotropic rotational relaxation studies of the purified and l...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00184a004
更新日期：1994-05-10 00:00:00
abstract：:Oxalate:ferredoxin oxidoreductase (OOR) is an unusual member of the thiamine pyrophosphate (TPP)-dependent 2-oxoacid:ferredoxin oxidoreductase (OFOR) family in that it catalyzes the coenzyme A (CoA)-independent conversion of oxalate into 2 equivalents of carbon dioxide. This reaction is surprising because binding of C...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.7b00222
更新日期：2017-06-06 00:00:00
abstract：:The effects of Ca2+, Mg2+, and troponin I (TnI) inhibitory peptide (Ip) binding on the spectral properties of a Phe-154 to Trp mutant (F154W) of chicken recombinant troponin C (rTnC) have been examined. Residue 154 is positioned in the final flanking helix H of metal binding site IV. Since there are no other Tyr or Tr...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00176a028
更新日期：1994-03-15 00:00:00
abstract：:15N-labeled hen lysozyme has been studied by 2D and 3D NMR in order to characterize its dynamic behavior. The resonances of all main-chain amide nitrogen atoms were assigned, as were resonances of nitrogen atoms in 28 side chains. Relaxation measurements for the main-chain and arginine and tryptophan side-chain 15N nu...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00012a023
更新日期：1995-03-28 00:00:00
abstract：:Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00215a025
更新日期：1991-01-08 00:00:00
abstract：:The genomic hypervariation of human immunodeficiency virus 1 (HIV-1) could result from misincorporations by the viral reverse transcriptase. We developed an assay for reverse transcriptase fidelity during RNA-dependent as well as DNA-dependent DNA polymerization in vitro. A lacZ alpha RNA fragment transcribed by T3 RN...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00119a002
更新日期：1992-02-04 00:00:00
abstract：:Although the importance of interactions involving both the cytosolic and transmembrane regions of SecY and SecE has been documented, no information has been available for the physical contact sites of these translocase subunits in their cytosolic domains. We now carried out site-specific cross-linking experiments to i...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034333v
更新日期：2003-06-24 00:00:00
abstract：:The unfolding and dissociation of the tetrameric enzyme fructose-1,6-bisphosphatase from pig kidney by guanidine hydrochloride have been investigated at equilibrium by monitoring enzyme activity, ANS binding, intrinsic (tyrosine) protein fluorescence, exposure of thiol groups, fluorescence of extrinsic probes (AEDANS,...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034203m
更新日期：2003-06-17 00:00:00
abstract：:Fructose-1,6-bisphosphate muscle aldolase is an essential glycolytic enzyme that catalyzes reversible carbon-carbon bond formation by cleaving fructose 1,6-bisphosphate to yield dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde phosphate. To elucidate the mechanistic role of conserved amino acid Asp-33, Asn-33 an...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi8021558
更新日期：2009-06-02 00:00:00
abstract：:Four different temperature-sensitive M protein mutants (tsM) of vesicular stomatitis virus (VSV) were characterized with regard to the association of the mutated M protein either with nucleocapsids or with membranes in the intact virions. Virions were labeled with the photoreactive hydrophobic probe [125I]iodonaphthyl...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00527a020
更新日期：1981-11-24 00:00:00
abstract：:The acid-base properties of ionophore A23187 in methanol-water solutions (0--95% w/w) and bound to unilamellar vesicles of dimyristoylphosphatidylcholine were examined by ultraviolet and fluorescence spectroscopy, and the spectral properties for the acidic and basic forms were defined under these conditions. Standard ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00539a023
更新日期：1982-05-11 00:00:00
abstract：:The role of interleukin-8 (IL-8) and related CXC chemokines has been demonstrated in many human diseases. However, more profound studies, e.g., by blocking the effect of these inflammatory mediators, request animal models and hence the identification of all human counterparts for commonly used laboratory animals. In t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0011227
更新日期：2000-11-28 00:00:00
abstract：:Human serum albumin (HSA) is the most abundant protein in the blood plasma and is involved in the transport of metal ions. Four metal-binding sites with different specificities have been described in HSA: (i) the N-terminal site provided by Asp1, Ala2, and His3, (ii) the site at the reduced Cys34, (iii) site A, includ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi061783p
更新日期：2007-02-27 00:00:00
abstract：:An improved procedure for the preparation of cobalt-cytochrome c has been developed. Various factors influencing the cobalt insertion process are discussed. The optical spectra of cobalt-cytochrome c suggest a six-coordinated species. The spectral shifts occurring with oxidation-reduction are compared with those obser...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00687a003
更新日期：1975-08-12 00:00:00
abstract：:Multivalent binding is an efficient means to enhance the affinity and specificity of chemical probes targeting multidomain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, physical and structural characterization of bivalent binding encounters m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.8b00150
更新日期：2018-04-10 00:00:00
abstract：:The fluorescence polarization intensities from fluorescent probes and the electron paramagnetic resonance spectra from spin probes, specifically modifying elements of a biological assembly such as myosin sulfhydryl 1 (SH1) in muscle fibers, are interpreted in terms of probe order parameters using a model-independent m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00116a029
更新日期：1992-01-14 00:00:00
abstract：:Phytochromes are widespread red/far-red photosensory proteins well known as critical regulators of photomorphogenesis in plants. It is often assumed that natural selection would have optimized the light sensing efficiency of phytochromes to minimize nonproductive photochemical deexcitation pathways. Surprisingly, the ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi500108s
更新日期：2014-05-06 00:00:00
abstract：:Hypoxic respiratory diseases or hypoxia exposures are frequently accompanied by glucose intolerance and impaired nitric oxide (NO) availability. However, the molecular mechanism responsible for impaired NO production and insulin resistance (IR) during hypoxia remains obscure. In this study, we investigated the possibl...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi401061e
更新日期：2014-01-14 00:00:00
abstract：:alpha-Conotoxin GI is a snail toxin protein consisting of 13 amino acids cross-linked by 2 intramolecular disulfide bridges. This toxin is an antagonist of acetylcholine receptors. The native sequence has been synthesized, along with nine additional variants in which non-cysteine residues are replaced by alanine or th...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00111a021
更新日期：1991-11-26 00:00:00
abstract：:Restrictocin and related fungal endoribonucleases from the α-sarcin family site-specifically cleave the sarcin/ricin loop (SRL) on the ribosome to inhibit translation and ultimately trigger cell death. Previous studies showed that the SRL folds into a bulged-G motif and tetraloop, with restrictocin achieving a specifi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi1018336
更新日期：2011-04-12 00:00:00
abstract：:Arachidonic acid metabolism by lipoxygenases and cytochrome P450 monooxygenases produces regioisomeric hydroperoxyeicosatetraenoic acids (HPETEs), hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs), which serve as components of cell signaling cascades. In...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi001602y
更新日期：2001-01-30 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
