Mary Koszelak‐Rosenblum

ORCID: 0000-0002-8210-8722
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About
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Research Areas
  • Pneumocystis jirovecii pneumonia detection and treatment
  • Pneumonia and Respiratory Infections
  • Biofuel production and bioconversion
  • Peroxisome Proliferator-Activated Receptors
  • Metal-Catalyzed Oxygenation Mechanisms
  • Bacterial Infections and Vaccines
  • Cellular transport and secretion
  • CRISPR and Genetic Engineering
  • Enzyme Structure and Function
  • Microbial Metabolic Engineering and Bioproduction
  • DNA Repair Mechanisms
  • Crystallization and Solubility Studies
  • Endoplasmic Reticulum Stress and Disease
  • Syphilis Diagnosis and Treatment
  • Chronic Kidney Disease and Diabetes
  • Fungal and yeast genetics research
  • Lysosomal Storage Disorders Research
  • Cancer-related gene regulation
  • Pharmacogenetics and Drug Metabolism
  • Microbial Natural Products and Biosynthesis
  • Microbial bioremediation and biosurfactants
  • Protein Structure and Dynamics
  • Polyoxometalates: Synthesis and Applications
  • Epigenetics and DNA Methylation
  • Diatoms and Algae Research

Albany Molecular Research (United States)
2020

Hauptman-Woodward Medical Research Institute
2008-2017

University at Buffalo, State University of New York
2013-2017

Posttranslational lipidation provides critical modulation of the functions some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X any residue). Isoprenylation followed by cleavage AAX amino acid and, cases, additional proteolytic cuts. We determined crystal structure protease Ste24p, a zinc metalloprotease catalyzing two steps maturation yeast mating...

10.1126/science.1232048 article EN Science 2013-03-28

Neuronal electrical impulse propagation is facilitated by the myelin sheath, a compact membrane surrounding axon. The sheath highly enriched in galactosylceramide (GalCer) and its sulfated derivative sulfatide. Over 50% of GalCer sulfatide hydroxylated integral enzyme fatty acid 2-hydroxylase (FA2H). hydroxylation contributes to nature membrane, mutations FA2H result debilitating leukodystrophies spastic paraparesis. We report here 2.6 Å crystal structure sphingolipid α-hydroxylase (Scs7p),...

10.1074/jbc.m115.680124 article EN cc-by Journal of Biological Chemistry 2015-10-30

ABSTRACT Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease adults, resulting significant worldwide morbidity mortality. M. has growth requirement for arginine; thus, acquiring arginine important fitness survival. putative oligopeptide permease ABC transport operon ( opp ) consisting five genes oppB , oppC oppD oppF oppA ), encoding two permeases, ATPases, substrate binding protein. Thermal shift...

10.1128/iai.02185-14 article EN Infection and Immunity 2014-08-26

ABSTRACT Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower infections adults with chronic obstructive pulmonary disease. We have identified characterized zinc uptake ABC transporter present all strains of M. tested. A mutant which the znu gene cluster knocked out shows markedly impaired growth compared to wild type medium contains trace zinc; restored wild-type levels by supplementing but not other divalent cations. Thermal-shift...

10.1128/iai.00589-13 article EN Infection and Immunity 2013-07-02

The endonuclease Artemis is responsible for opening DNA hairpins during V(D)J recombination and processing a subset of pathological double-strand breaks. an attractive target the development therapeutics to manage various B cell T tumors, because failure open accumulation chromosomal breaks may reduce proliferation viability pre-T pre-B derivatives. However, structure-based drug discovery specific inhibitors has been hampered by lack crystal structures. Here, we report structure catalytic...

10.1074/jbc.ra120.014136 article EN cc-by Journal of Biological Chemistry 2020-06-24

Elucidating the structures of membrane proteins is essential to our understanding disease states and a critical component in rational design drugs. Structural characterization protein begins with its detergent solubilization from lipid bilayer purification within functionally stable protein-detergent complex (PDC). Crystallization PDC typically occurs by changing solution environment decrease solubility promote interactions between exposed hydrophilic surface residues. As have been observed...

10.1002/pro.193 article EN Protein Science 2009-06-24

α-Dioxygenases (α-DOX) oxygenate fatty acids into 2(R)-hydroperoxides. Despite the low level of sequence identity, α-DOX share common catalytic features with cyclooxygenases (COX), including use a tyrosyl radical during catalysis. We determined X-ray crystal structure Arabidopsis thaliana to 1.5 Å resolution. The is monomeric, predominantly α-helical, and comprised two domains. base domain exhibits degree structural homology membrane-binding COX but lies in similar position respect domain....

10.1021/bi400013k article EN Biochemistry 2013-02-01

Structural crystallography aims to provide a three-dimensional representation of macromolecules. Many parts the multistep process produce structural model have been automated, especially through various genomics projects. A key step is production crystals for diffraction. The target macromolecule combined with large and chemically diverse set cocktails some leading ideally, but infrequently, crystallization. variety outcomes will be observed during these screening experiments that typically...

10.1107/s0907444908028047 article EN Acta Crystallographica Section D Biological Crystallography 2008-10-17

Pathogen-inducible oxygenase (PIOX) oxygenates fatty acids into 2R-hydroperoxides. PIOX belongs to the acid alpha-dioxygenase family, which exhibits homology cyclooxygenase enzymes (COX-1 and COX-2). Although these share common catalytic features, including use of a tyrosine radical during catalysis, little is known about other residues involved in dioxygenase reaction PIOX. We generated model linoleic (LA) bound based on computational sequence alignment secondary structure predictions with...

10.1074/jbc.m804358200 article EN cc-by Journal of Biological Chemistry 2008-07-03

α-Dioxygenases (α-DOX) are heme-containing enzymes found predominantly in plants and fungi, where they generate oxylipins response to pathogen attack. α-DOX oxygenate a variety of 14-20 carbon fatty acids containing up three unsaturated bonds through stereoselective removal the pro-R hydrogen from α-carbon by tyrosyl radical generated via oxidation heme moiety peroxide (H2 O2 ). We determined X-ray crystal structures wild type Oryza sativa, enzyme complex with H2 , catalytically inactive...

10.1002/pro.2327 article EN Protein Science 2013-08-12

The protein kinase R (PKR)-like endoplasmic reticulum (PERK) is one of the three (ER) transmembrane sensors unfolded response (UPR) that regulates synthesis, alleviates cellular ER stress and has been implicated in tumorigenesis prolonged cancer cell survival. In this study, we report a series 2-amino-3-amido-5-aryl-pyridines have identified as potent, selective, orally bioavailable PERK inhibitors. Amongst studied herein, compound (28)...

10.1016/j.bmcl.2021.128058 article EN cc-by-nc-nd Bioorganic & Medicinal Chemistry Letters 2021-04-23

Moraxella catarrhalis is an exclusively human pathogen that important cause of otitis media in children and lower respiratory tract infections adults with chronic obstructive pulmonary disease. A vaccine to prevent M. would have enormous global impact reducing morbidity resulting from these infections. Substrate binding protein 2 (SBP2) ABC transporter system has recently been identified as a promising candidate antigen on the bacterial surface catarrhalis. In this study, we showed SBP1, -2,...

10.1128/iai.00799-15 article EN Infection and Immunity 2015-11-24

is an exclusively human respiratory tract pathogen that a common cause of otitis media in children and infections adults with chronic obstructive pulmonary disease. A vaccine to prevent these would have major impact on reducing the substantial global morbidity mortality populations. Through genome mining approach, we identified AfeA, ∼32-kDa substrate binding protein ABC transport system, as excellent candidate antigen. Recombinant AfeA was expressed purified binds ferric, ferrous,...

10.1128/cvi.00130-17 article EN Clinical and Vaccine Immunology 2017-06-29
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