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Marilyn Jorns

Marilyn Jorns, PhD

Professor


Department: Biochemistry & Molecular Biology

Education

  • PhD in Biochemistry - University of Michigan (1970)

Dr. Jorns is a professor in the Department of Biochemistry & Molecular Biology at Drexel University College of Medicine.

Research Overview

Research Interests: Metabolism and regulation of biological signaling molecules, mechanism and structural basis of enzyme catalysis.

Research Interests

Metabolism and regulation of biological signaling molecules, mechanism and structural basis of enzyme catalysis.

Research

Hydrogen sulfide (H2S) is the only gasotransmitter that is enzymatically metabolized and the only inorganic compound that can be used by mammals to generate ATP. Until recently, H2S was the least appreciated of the three known gasotransmitters, but new evidence suggests that it may emerge as the most important one. H2S signaling is involved in numerous cellular processes and plays an especially important role in the cardiovascular system. Despite its multiple life-supporting properties, H2S is a Janus-faced molecule that can exhibit toxic effects at abnormally high or low concentrations. For example, a genetic defect in the mitochondrial metabolism of H2S is the cause of ethylmalonic encephalopathy, a devastating, invariably fatal disorder of infancy that is characterized by extremely high (toxic) levels of the gasotransmitter. In contrast, clinical data and animal model studies provide compelling evidence for a functional association between abnormally low levels of H2S and cardiovascular disease.

The proposed scheme for mammalian metabolism of H2S features two alternate termination steps to account for observed tissue differences in the final product. SQOR, sulfide:quinone oxidoreductase; TST, thiosulfate:glutathione sulfurtransferase; SDO, sulfer dioxygenase; SO, sulfite oxidase.

Our long-term goals are to elucidate the pathways for and regulation of the mitochondrial metabolism of H2S, and to apply this knowledge to treat defects in H2S metabolism. Sulfide:quinone oxidoreductase (SQOR) is an integral membrane flavoprotein that catalyzes the first irreversible step in H2S metabolism and, as such, sits at a key potential regulatory point. We are studying the catalytic mechanism of this important enzyme and investigating its possible regulation by posttranslational modification. Our identification of sulfite (SO3-2) as the physiological acceptor of the sulfane sulfur (S0) produced in the SQOR reaction has necessitated a major revision of previously proposed pathways for H2S metabolism. The new model accounts for the downstream metabolism of the thiosulfate (SSO3-2) product of the SQOR reaction and observed tissue differences in H2S metabolism (see figure). Studies to evaluate the new metabolic scheme are in progress. Our research strategy is multifaceted and encompasses numerous experimental strategies, including cell-based metabolic assays, high-throughput screening techniques, recombinant protein expression, X-ray crystallography and single turnover studies with ultra-fast spectroscopic detection.

Publications

"Role of Human Sulfide:quinone Oxidoreductase in H2S Metabolism"
ML Jackson, SL Melideo, and MS Jorns
Methods Enzymol., in press

"Biosynthesis of a Central Intermediate in Hydrogen Sulfide Metabolism by a Novel Human Sulfurtransferase and its Yeast Ortholog"
SL Melideo, ML Jackson, and MS Jorns
Biochemistry, 53, 4739-4753 (2014)

“Toward Understanding the Mechanism of Oxygen Activation by Flavoprotein Oxidases”
M. S. Jorns

Handbook of Flavoproteins
(Hille R, Miller SM and Palfey B eds.), De Gruyter, Berlin, pp 195-211 (2013)

"Human Sulfide:quinone Oxidoreductase Catalyzes the First Step in Hydrogen Sulfide Metabolism and Produces a Sulfane Sulfur Metabolite"
ML Jackson, SL Melideo, and MS Jorns
Biochemistry, 51, 6804-6815 (2012)

"Probing Oxygen Activation Sites in Two Flavoprotein Oxidases Using Chloride as an Oxygen Surrogate"
PR Kommoju, Z Chen, RC Bruckner, FS Mathews, and MS Jorns 
Biochemistry, 50, 4949-4962 (2011)

"Pleiotropic Impact of a Single Lysine Mutation on Biosynthesis of and Catalysis by N-Methyltryptophan oxidase"
RC Bruckner, J Winans, and MS Jorns
Biochemistry, 50, 4949-4962 (2011)

"Structural Characterization of the Oxygen Activation Site in Monomeric Sarcosine Oxidase"
MS Jorns, Z Chen, and FS Mathews
Biochemistry, 49, 3631-3639 (2010)

"Factors that Affect Oxygen Activation and Coupling of the Two Redox Cycles in the Aromatization Reaction Catalyzed by NikD, an Unusual Amino Acid Oxidase"
PR Kommoju, RC Bruckner, P Ferreira, CJ Carrell, FS Mathews and MS Jorns
Biochemistry, 48, 9542-9555 (2009)

"Probing the Role of Active Site Residues in NikD, an Unusual Amino Acid Oxidase that Catalyzes an Aromatization Reaction Important in Nikkomycin Biosynthesis"
PR Kommoju, RC Bruckner, P Ferreira and MS Jorns
Biochemistry, 48, 6951-6962 (2009)

"Spectral and Kinetic Characterization of Intermediates in the Aromatization Reaction Catalyzed by NikD, an Unusual Amino Acid Oxidase"
RC Bruckner, and MS Jorns
Biochemistry, 48, 4455-4465 (2009)

"Identification of the Oxygen Activation Site in Monomeric Sarcosine Oxidase: Role of Lys265 in Catalysis"
G Zhao, RC Bruckner, and MS Jorns
Biochemistry, 47, 9124-9135 (2008)

"Covalent Flavinylation of Monomeric Sarcosine Oxidase: Identification of a Residue Essential for Holoenzyme Biosynthesis"
A Hassan-Abdallah, G Zhao and MS Jorns
Biochemistry, 47, 1136-1143 (2008)

"Arginine 49 is a Bifunctional Residue Important in Catalysis and Biosynthesis of Monomeric Sarcosine Oxidase: A Context-sensitive Model for the Electrostatic Impact of Arginine to Lysine Mutations"
A Hassan-Abdallah, G Zhao, Z Chen, FS Mathews and MS Jorns
Biochemistry, 47, 2913-2922 (2008)

"NikD, an Unusual Amino Acid Oxidase Essential for Nikkomycin Biosynthesis"
CJ Carrell, RC Bruckner, D Venci, G Zhao, MS Jorns and FS Mathews
Structure, 15, 928-941 (2007)

"A Mobile Tryptophan is the Intrinsic Charge Transfer donor in a Flavoenzyme Essential for Nikkomycin Antibiotic Biosynthesis"
RC Bruckner, G Zhao, P Ferreira and MS Jorns
Biochemistry, 46, 819-827 (2007)

"Heterotetrameric Sarcosine Oxidase: Structure of a Diflavin Metalloenzyme at 1.85 Å Resolution"
Z Chen, A Hassan-Abdallah, G Zhao, MS Jorns and FS Mathews
J. Mol. Biol., 360, 1000-1018 (2006)

"Biosynthesis of Covalently Bound Flavin: Isolation and in vitro Flavinylation of the Monomeric Sarcosine Oxidase Apoprotein"
A Hassan-Abdallah, RC Bruckner, GH Zhao and MS Jorns
Biochemistry, 44, 6452-6462 (2005)


Contact Information


Research Office

Department of Biochemistry & Molecular Biology
245 North 15th Street
Mail Stop 497
Philadelphia, PA 19102
Phone: 215.762.7495
Fax: 215.762.4452