CHEM Faculty Publications

Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor

Perera, Krishani Dinali; Rathnayake, Athri D.; Liu, Hongwei; Pedersen, Niels C.; Groutas, William C.; Chang, Kyeong-Ok; Kim, Yunjeong (Elsevier, 2019-10)

Feline infectious peritonitis (FIP) is a highly fatal disease caused by a virulent feline coronavirus in domestic and wild cats. We have previously reported the synthesis of potent coronavirus 3C-like protease (3CLpro) ...

Ion mobility spectrometry of macromolecules with dipole alignment switchable by varying the gas pressure

Shvartsburg, Alexandre A.; Andrzejewski, Roch; Entwistle, Andrew; Giles, Roger (American Chemical Society, 2019-06-05)

Since inception in the 1980s, differential or field asymmetric waveform ion mobility spectrometry (FAIMS) was implemented at or near the ambient gas pressure (AP). Recently, we developed FAIMS at 15-30 Torr within a mass ...

Protein solvent shell structure provides rapid analysis of hydration dynamics

Dahanayake, Jayangika Niroshani; Shahryari, Elaheh; Roberts, Kirsten M.; Heikes, Micah E.; Kasireddy, Chandana; Mitchell-Koch, Katie R. (American Chemical Society, 2019-03-13)

The solvation layer surrounding a protein is clearly an intrinsic part of protein structure-dynamics-function, and our understanding of how the hydration dynamics influences protein function is emerging. We have recently ...

High-resolution differential ion mobility separations/orbitrap mass spectrometry without buffer gas limitations

Baird, Matthew A.; Shliaha, Pavel V.; Anderson, Gordon A.; Moskovets, Eugene; Laiko, Victor; Makarov, Alexander A.; Jensen, Ole N.; Shvartsburg, Alexandre A. (American Chemical Society, 2019-04-29)

Strong orthogonality between differential ion mobility spectrometry (FAIMS) and mass spectrometry (MS) makes their hybrid a powerful approach to separate isomers and isobars. Harnessing that power depends on high resolution ...

N-methyl-4-phenylpyridinium scaffolds containing lipophilic compounds are potent complex i inhibitors and selective dopaminergic toxins

Lickteig, Bryan; Wimalasena, Virangika K.; Wimalasena, Kandatege (ACS, 2019-04-01)

Although the exact cause or causes of Parkinson's disease (PD) are not fully understood, it is believed that environmental factors play a major role. The discovery that a synthetic chemical, 1-methyl-4-phenyl-1,2,3,6-tet ...

Putative structural rearrangements associated with the interaction of macrocyclic inhibitors with norovirus 3CL protease

Galasiti Kankanamalage, Anushka; Weerawarna, Pathum M.; Rathnayake, Athri D.; Kim, Yunjeong; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Chang, Kyeong-Ok; Groutas, William C. (John Wiley and Sons, 2019-03-18)

Human noroviruses are the primary cause of outbreaks of acute gastroenteritis worldwide. The problem is further compounded by the current lack of norovirus-specific antivirals or vaccines. Noroviruses have a single-stranded, ...

Exploring one-state downhill protein folding in single molecules

Liu, Jianwei; Campos, Luis A.; Cerminara, Michele; Wang, Xiang; Ramanathan, Ravishankar; English, Douglas S.; Munoz, Victor (National Academy of Sciences, 2012-01-3)

A one-state downhill protein folding process is barrierless at all conditions, resulting in gradual melting of native structure that permits resolving folding mechanisms step-by-step at atomic resolution. Experimental ...

Catalysis of protein folding by chaperones in pathogenic bacteria

Bann, James G.; Pinkner, Jerome S.; Frieden, Carl; Hultgren, Scott J. (2004-12-14)

Molecular chaperones are thought to inhibit off-pathway interactions such as aggregation from occurring without influencing the on-pathway formation of native structure. Here, we present a mechanism whereby the family of ...

Altered acetylcholinesterase activity (AChE) and maze performance of developing rats (Rattus norvegicus) following mesencephalic electrical brain stimulation

Lewis, George A.; Preskorn, Sheldon H.; Hughes, Carroll W. (Springer-Verlag, 1977-11-17)

Cortical arousal was altered by electrical brain stimulation (EBS) to the mesencephalic ascending reticular formation beginning at 27 days of age and administered 2 h/day for either 14 or 28 days. Subjects receiving brain ...

Evolution of stability/flexibility relationships in beta-lactamase

Patterson, John; Tsilimigras, Matthew C. B.; Livesay, Dennis R.; Jacobs, Donald J. (Cell Press, 2019-02-15)

We have curated over 100 structures of class A beta-lactamase proteins, a family of enzymes that is responsible for a considerable percentage of multidrug antibiotic resistance in bacteria. Our dataset includes three ...

Characterizing dynamical differences between TEM-1 and TEM-52 beta-lactamases

Avery, Christopher; Farmer, Jenny; Tsilimigras, Matthew C. B.; David, Charles; Livesay, Dennis R.; Jacobs, Donald J. (Cell Press, 2019-02-15)

Beta-lactamase, produced in bacteria, defends against beta-lactam antibiotics such as penicillin and cephalosporins by hydrolyzing the beta-lactam ring. This is a primary cause of antibiotic resistance to beta-lactam ...

Antiviral drug discovery: norovirus proteases and development of inhibitors

Chang, Kyeong-Ok; Kim, Yunjeong; Lovell, Scott; Rathnayake, Athri D.; Groutas, William C. (MDPI AG, Basel, Switzerland, 2019-02-25)

Proteases are a major enzyme group playing important roles in a wide variety of biological processes in life forms ranging from viruses to mammalians. The aberrant activity of proteases can lead to various diseases; ...

Elemental dependence of structurally specific isotopic shifts in high-field ion mobility spectra

Baird, Matthew A.; Pathak, Pratima; Shvartsburg, Alexandre A. (ACS, 2019-02-01)

Nearly all molecules incorporate at least one element with stable isotopes, yielding ubiquitous isotopologic envelopes in mass spectra. Those envelopes split in differential or field asymmetric waveform ion mobility (FAIMS) ...

Periplasmic peptidyl prolyl cis-trans isomerases are not essential for viability, but SurA is required for pilus biogenesis in Escherichia coli

Justice, Sheryl S.; Hunstad, David A.; Harper, Jill R.; Duguay, Amy R.; Pinkner, Jerome S.; Bann, James G.; Frieden, Carl; Silhavy, Thomas J.; Hultgren, Scott J. (American Society for Microbiology, 2005-08-31)

In Escherichia coli, FkpA, PpiA, PpiD, and SurA are the four known periplasmic cis-trans prolyl isomerases. These isomerases facilitate proper protein folding by increasing the rate of transition of proline residues between ...