A5040033989- Antimicrobial Resistance in Staphylococcus
- Veterinary medicine and infectious diseases
- Nitric Oxide and Endothelin Effects
- Ion Transport and Channel Regulation
- Receptor Mechanisms and Signaling
- Biochemical and Structural Characterization
- Phosphodiesterase function and regulation
- Infective Endocarditis Diagnosis and Management
- Magnesium in Health and Disease
- Pharmacological Effects of Natural Compounds
- Protein Kinase Regulation and GTPase Signaling
- T-cell and B-cell Immunology
- Enzyme function and inhibition
- Crystallography and molecular interactions
- Pneumonia and Respiratory Infections
- Mycobacterium research and diagnosis
- Signaling Pathways in Disease
- Advanced biosensing and bioanalysis techniques
- Aquatic Ecosystems and Phytoplankton Dynamics
- Renin-Angiotensin System Studies
- Mechanisms of cancer metastasis
- Trace Elements in Health
- Hormonal Regulation and Hypertension
- Microtubule and mitosis dynamics
- Cancer Immunotherapy and Biomarkers
Bristol-Myers Squibb (United States)
2025
University of Arizona
2018-2019
University of Vermont
2013-2018
The University of Texas Southwestern Medical Center
2007-2014
Southwestern Medical Center
2012
Structural analysis reveals how chloride inhibits the activation of a kinase implicated in hypertension.
The final steps of cell-wall biosynthesis in bacteria are carried out by penicillin-binding proteins (PBPs), whose transpeptidase domains form the cross-links peptidoglycan chains that define bacterial cell wall. These enzymes targets β-lactam antibiotics, as their inhibition reduces structural integrity Bacterial resistance to antibiotics is a rapidly growing concern; however, underpinnings PBP-derived antibiotic poorly understood. PBP4 and PBP5 low-affinity, class B transpeptidases confer...
Testing of candidate monoclonal antibody therapeutics in preclinical models is an essential step drug development. Identification therapeutic candidates that bind their human targets and cross-react to mouse orthologs often challenging, especially for with low sequence homology. In such cases, surrogate antibodies must be used. The 9D9, which binds CTLA-4, a commonly used CTLA-4 checkpoint blockade studies cancer models. this work, we reveal 9D9 has significant biophysical dissimilarities...
Enterococcus faecalis strains resistant to penicillin and ampicillin are rare have been associated with increases in quantities of low-affinity penicillin-binding protein 4 (PBP4) or amino acid substitutions PBP4. We report an E. strain (LS4828) isolated from a prosthetic knee joint that was subjected long-term exposure aminopenicillins. Subsequent cultures yielded MICs penicillins carbapenems higher than those for wild-type JH2-2. Sequence analysis the pbp4 gene LS4828 compared JH2-2...
The metalloenzyme protein phosphatase 1 (PP1), which is responsible for ≥50% of all dephosphorylation reactions, regulated by scores regulatory proteins, including the highly conserved SDS22 protein. has numerous diverse functions, surprisingly acting as both a PP1 inhibitor and an activator. Here, we integrate cellular, biophysical, crystallographic studies to address this conundrum. We discovered that selectively binds unique conformation contains single metal (M2) at its active site,...
The Phosphoprotein Phosphatase Calcineurin (CN, PP2B, PP3) recognizes and binds to two short linear motifs (SLiMs), PxIxIT LxVP, in its regulators substrates. These interactions enable CN function many key biological processes. identification of SLiMs is difficult because their short, degenerate sequence often low binding affinity. Here we combine Structure Based Shape Complementarity (SBSC) analysis proteome-wide affinity purification-mass spectrometry identify LxVP containing interactors...
Cellular retinoic acid-binding protein 2 (CRABP2) delivers all-trans acid (atRA) to receptors (RARs), allowing for the activation of specific gene transcription. The structural similarities between free and atRA-bound CRABP2 raise questions how atRA binding occurs atRA:CRABP2 complex is recognized by downstream partners. Thus, gain insights into these questions, we conducted a detailed atRA–CRABP2 interaction study using nuclear magnetic resonance spectroscopy. data showed that displays...
The type I cGMP-dependent protein kinases (PKG I) serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating cooperative activation. Previous investigations into the activation mechanisms of PKG isoforms have been largely influenced by structures cAMP-dependent kinase (PKA). Here, we examined Iα cGMP cAMP engineering...
This research focuses on a 230kDa serine/threonine protein kinase known as WNK1 (With No lysine {K}), isoforms of which have been associated with monogenic form hypertension. Structural analysis the autoinhibitory (AI) domain from by NMR indicates that RFXV binding site PASK/FRAY homology 2 (PF2) is conserved in AI domain. Titration data shows incubation peptides display extensive chemical shift perturbation assessed 1 H, 15 N‐HSQC. Size exclusion chromatography tethered construct and...