A5065012856- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Vitamin K Research Studies
- Immunotherapy and Immune Responses
- Carbon dioxide utilization in catalysis
- Glycosylation and Glycoproteins Research
- Synthesis of heterocyclic compounds
- Synthesis and Characterization of Heterocyclic Compounds
- Chemical Synthesis and Reactions
- Protein Structure and Dynamics
- Erythrocyte Function and Pathophysiology
- Protein Tyrosine Phosphatases
- SARS-CoV-2 and COVID-19 Research
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- Cell Adhesion Molecules Research
- Parasites and Host Interactions
- T-cell and B-cell Immunology
- Biochemical and Molecular Research
- HIV Research and Treatment
- Synthesis and biological activity
- Proteoglycans and glycosaminoglycans research
Yale University
2015-2025
University of New Haven
2023
Yale Cancer Center
2010-2020
IE University
2019
University School
2019
Berry (United States)
2015
Icahn School of Medicine at Mount Sinai
2012
Baoshan College
2010
Seagen (United States)
2002
Vanderbilt University
2002
Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in near selectivity filter potassium (K(+)) channel KCNJ5 that present 8 22 human APAs studied. Both produce increased sodium (Na(+)) conductance depolarization, which glomerulosa cells produces calcium (Ca(2+)) entry,...
Macrophage migration inhibitory factor (MIF) was the first cytokine to be described, but for 30 years its role in immune response remained enigmatic. In recent studies, MIF has been found a novel pituitary hormone and protein identified released from cells on glucocorticoid stimulation. Once secreted, counterregulates immunosuppressive effects of steroids thus acts as critical component system control both local systemic responses. We report herein x-ray crystal structure human 2.6 angstrom...
Macrophage migration inhibitory factor (MIF) is an immunoregulatory protein that a potential therapeutic target for number of inflammatory diseases. Evidence exists unexpected catalytic active site MIF may have biological function. To gain further insight into the role site, series mutational, structural, and activity studies were performed. The insertion alanine between Pro-1 Met-2 (PAM) abolishes non-physiological activity, this mutant defective in vitro glucocorticoid counter-regulatory...
The structure of yeast triosephosphate isomerase (TIM) has been solved at 3.0-A resolution and refined 1.9-A to an R factor 21.0%. final model consists all non-hydrogen atoms in the polypeptide chain 119 water molecules, a number which are found interior protein. active site clearly indicates that carboxylate catalytic base, Glu 165, is involved hydrogen-bonding interaction with hydroxyl Ser 96. In addition, interactions other residues, Lys 12 His 95, also discussed. For first time any TIM...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-.ANG. resolution: implications for catalysisElias Lolis Gregory A. PetskoCite this: Biochemistry 1990, 29, 28, 6619–6625Publication Date (Print):July 17, 1990Publication History Published online1 May 2002Published inissue 17 July 1990https://pubs.acs.org/doi/10.1021/bi00480a010https://doi.org/10.1021/bi00480a010research-articleACS...
Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion MIF does not completely abrogate activation responses, however, and receptor, CD74, produces more pronounced phenotype than deficiency. We hypothesized that these observations may be explained by second MIF-like ligand, we considered probable candidate to protein encoded homologous, D -dopachrome tautomerase (D-DT) gene. show recombinant D-DT binds CD74 with high...
AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used cerebrovascular and ocular indications. It a nonselective inhibitor various phosphodiesterases (PDEs) varied activity. More recently, studied as possible therapeutic neuropathic pain opioid withdrawal through its actions on glial cells. As described herein, PDE PDE-inhibition-compromised analog AV1013...
CXCL12 (SDF-1α) and CXCR4 are critical for embryonic development cellular migration in adults. These proteins involved HIV-1 infection, cancer metastasis, WHIM disease. Sequestration presentation of to by glycosaminoglycans (GAGs) is proposed be important receptor activation. Mutagenesis has identified residues that bind heparin. However, the molecular details this interaction have not yet been determined. Here we demonstrate soluble heparin heparan sulfate negatively affect CXCL12-mediated...
Although chemokine and growth factor receptors are attractive popular targets for cancer therapeutic intervention, structure-based targeting of the ligands themselves is generally not considered practical. New evidence indicates that a notable exception to this macrophage migration inhibitory (MIF). MIF, an autocrine- paracrine-acting cytokine/growth factor, plays pivotal role in both initiation maintenance neoplastic diseases. MIF possesses nonphysiologic enzymatic activity evolutionarily...
Significance CD74 has been associated with tumor progression and metastasis. Its expression suggested to serve as a prognostic factor in many cancers, higher relative behaving marker of progression. Our previous studies showed that stimulation expressed on chronic lymphocytic cells initiates signaling cascade leading survival. The present study demonstrates CD74’s cytoplasmic domain binds chromatin regulates transcription genes involved immune regulation, cell survival, hematopoietic...
Autoimmunity leads to the activation of innate effector pathways, proinflammatory cytokine production, and end-organ injury. Macrophage migration inhibitory factor (MIF) is an upstream activator response that mediates recruitment retention monocytes via CD74 associated chemokine receptors, it has a role in maintenance B lymphocytes. High-expression MIF alleles also are with damage different autoimmune diseases. We assessed therapeutic efficacy...
We present a previously undescribed initiative and its application, namely the design of molecularly imprinted polymers (MIPs) for producing protein crystals that are essential determining high-resolution 3D structures proteins. MIPs, also referred to as "smart materials," made contain cavities capable rebinding protein; thus fingerprint created on polymer allows it serve an ideal template crystal formation. have shown six different MIPs induced crystallization nine proteins, yielding in...
Macrophage migration inhibitory factor (MIF) is an important immunoregulatory molecule with a unique ability to suppress the anti-inflammatory effects of glucocorticoids. Although considered cytokine, MIF possesses three-dimensional structure and active site similar those 4-oxalocrotonate tautomerase 5-carboxymethyl-2-hydroxymuconate isomerase. Moreover, number catalytic activities have been defined for MIF. To gain insight into role catalysis in biological function MIF, we begun...
Stromal cell-derived factor-1α (SDF-1α ) is a member of the chemokine superfamily and functions as growth factor chemoattractant through activation CXCR4/LESTR/Fusin, G protein-coupled receptor. This receptor also coreceptor for T-tropic syncytium-inducing strains HIV-1. SDF-1α antagonizes infectivity these by competing with gp120 binding to The crystal structure variant ([N33A]SDF-1α prepared total chemical synthesis has been refined 2.2-Å resolution. Although adopts typical β-β-β-α...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral discrimination in the covalent binding of bis(phenanthroline)dichlororuthenium(II) to B-DNAJacqueline K. Barton and Elias LolisCite this: J. Am. Chem. Soc. 1985, 107, 3, 708–709Publication Date (Print):February 1, 1985Publication History Published online1 May 2002Published inissue 1 February 1985https://pubs.acs.org/doi/10.1021/ja00289a035https://doi.org/10.1021/ja00289a035research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophilic catalysis in triosephosphate isomerase: the role of histidine-95Elizabeth A. Komives, Louise C. Chang, Elias Lolis, Robert F. Tilton, Gregory Petsko, and Jeremy R. KnowlesCite this: Biochemistry 1991, 30, 12, 3011–3019Publication Date (Print):March 26, 1991Publication History Published online1 May 2002Published inissue 26 March 1991https://pubs.acs.org/doi/10.1021/bi00226a005https://doi.org/10.1021/bi00226a005research-articleACS...
Abstract Parasitic organisms have evolved specialized strategies to evade immune defense mechanisms. We describe herein an ortholog of the cytokine, macrophage migration inhibitory factor (MIF), which is produced by obligate intracellular parasite, Leishmania major. The MIF protein, Lm1740MIF, shows significant structural homology with human as revealed a high-resolution x-ray crystal structure (1.03 Å). Differences between two proteins in N-terminal tautomerization site are evident, and we...
The inability to acquire protective immunity against Plasmodia is the chief obstacle malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria characterized by a highly inflammatory cytokine milieu, lack of effective protection infection suggests that memory T cells are not adequately formed or maintained. Using genetically targeted strain Plasmodium berghei, we observed ortholog macrophage migration inhibitory factor enhanced production also...
An emerging number of non-chemokine mediators are found to bind classical chemokine receptors and elicit critical biological responses. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that exhibits chemokine-like activities through non-cognate interactions with the CXCR2 CXCR4, in addition activating type II receptor CD74. Activation MIF-CXCR2 -CXCR4 axes promotes leukocyte recruitment, mediating exacerbating role MIF atherosclerosis contributing wealth other...
We report a new inflammatory activity for extracellular D-dopachrome tautomerase (D-DT), the recruitment of neutrophils to lung on D-DT intratracheal installation C57BL/6J mice with an EC50 5.6 μg. also find that and macrophage migration inhibitory factor (MIF) have additive effects in neutrophil recruitment. Although site its homologue MIF are biophysically very different, 4-iodo-6-phenylpyrimidine (4-IPP) forms co-valent bond Pro-1 both proteins, resulting 6-phenylpyrimidine (6-PP) adduct....