Kathleen P Howard

Learn More
Although previous studies are beginning to point to the specific types of helix-helix interactions that stabilize the folds of membrane-bound helical proteins, quantitative thermodynamic data on natural membrane proteins has been very limited. Here the database is expanded substantially by adding thermodynamic data for a series of sequence variants of M2(More)
The M2 protein from influenza A virus is a 97-amino-acid protein with a single transmembrane helix that forms proton-selective channels essential to virus function. The hydrophobic transmembrane domain of the M2 protein (M2TM) contains a sequence motif that mediates the formation of functional tetramers in membrane environments. A variety of structural(More)
The M2 protein from influenza A is a pH-activated proton channel that plays an essential role in the viral life cycle and serves as a drug target. Using spin labeling EPR spectroscopy, we studied a 38-residue M2 peptide spanning the transmembrane region and its C-terminal extension. We obtained residue-specific environmental parameters under both high- and(More)
As a target of antiviral drugs, the influenza A M2 protein has been the focus of numerous structural studies and has been extensively explored as a model ion channel. In this study, we capitalize on the expanding body of high-resolution structural data available for the M2 protein to design and interpret site-directed spin-labeling electron paramagnetic(More)
Interactions of membrane anchored molecules such as glycolipids with a membrane surface are important in determining headgroup conformation. It is therefore essential to represent these membrane surface interactions in molecular modeling studies of glycolipids and other membrane bound molecules. We introduce here an energy term that represents the(More)
We report NMR data for magnetically oriented phospholipid bilayers which have been doped with a lipid derivatized with a polyethylene glycol polymer headgroup to stabilize samples against aggregation. (13)C, (31)P, and (2)H NMR data indicate that the incorporation of PEG2000-PE (1% molar to DMPC) does not interfere with the orientation properties of(More)
Doxorubicin (DOX) is a potent anthracycline cancer drug whose interaction with anionic membrane phospholipids, such as cardiolipin (CL), is thought to contribute to its cytotoxicity as well as induce cardiotoxic side effects. We have studied the interaction of DOX with a CL containing model membrane system using high resolution, oriented sample (31)P and(More)
A method is presented for determining the average glycosidic torsion angles and motion about those angles for a glycolipid headgroup at a model membrane surface. Dipolar and quadrupolar coupling constants were previously collected on the headgroup of beta-dodecyl glucoside embedded in phospholipid/detergent bilayers which orient in a magnetic field(More)