- Amino Acid Enzymes and Metabolism
- Enzyme Production and Characterization
- Polyamine Metabolism and Applications
- Autophagy in Disease and Therapy
- Enzyme Structure and Function
- Cellular transport and secretion
- Phytochemistry and Bioactivity Studies
- Malaria Research and Control
- Mitochondrial Function and Pathology
- Virus-based gene therapy research
- Barrier Structure and Function Studies
- Cannabis and Cannabinoid Research
- Iron Metabolism and Disorders
- Methemoglobinemia and Tumor Lysis Syndrome
- Neonatal Health and Biochemistry
- Protein Structure and Dynamics
- Pharmacological Effects of Natural Compounds
- ATP Synthase and ATPases Research
- Neurotransmitter Receptor Influence on Behavior
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- CAR-T cell therapy research
- Animal Virus Infections Studies
- Hemoglobinopathies and Related Disorders
- Phytase and its Applications
Pennsylvania State University
2008-2024
Penn State Milton S. Hershey Medical Center
2005-2022
Hershey (United States)
2013
Brookhaven National Laboratory
1999-2006
University of South Florida
2001-2003
Florida College
2003
Moffitt Cancer Center
2001
University of Vermont
1998-2000
Massey University
1996-2000
University of British Columbia
1998-2000
The structures of the trigonal crystal form bovine β-lactoglobulin variant A at pH 6.2, 7.1, and 8.2 have been determined by X-ray diffraction methods a resolution 2.56, 2.24, 2.49 Å, respectively. corresponding values for R (Rfree) are 0.192 (0.240), 0.234 (0.279), 0.232 (0.277). C N termini as well two disulfide bonds clearly defined in these models. glutamate side chain residue 89 is buried 6.2 becomes exposed 7.1 8.2. This conformational change, involving loop 85−90, provides structural...
Binding of virus particles to specific host cell surface receptors is known be an obligatory step in infection even though the molecular basis for these interactions not well characterized. The crystal structure adenovirus fiber knob domain complex with I its human cellular receptor, coxsackie and receptor (CAR), presented here. Surface-exposed loops on contact one face CAR, forming a high-affinity complex. Topology mismatches between interacting surfaces create interfacial solvent-filled...
The N-lobe of human serum transferrin (hTF/2N) has been expressed in baby hamster kidney cells and crystallized both orthorhombic (P212121) tetragonal (P41212) space groups. Both crystal forms diffract to high resolution (1.6 1.8 A, respectively) have solved by molecular replacement. Subsequent refinement resulted final models for the structure hTF/2N that had crystallographic R-factors 18.1 19.7% two forms, respectively; these represent highest-resolution structures determined date....
Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with life-threatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction monitoring acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation the context catabolic stress associated non-specific illness. The mechanisms underlying this injury are poorly understood. Using recently...
Serum transferrin binds ferric ions in the bloodstream and transports them to cells, where they are released a process involving receptor-mediated endocytosis. Iron release is believed be pH dependent coupled with large conformational change. To help define steps iron release, we have determined three-dimensional structure of iron-free (apo) form recombinant N-lobe half-molecule human serum (ApoTfN) by X-ray crystallography. Two crystal forms were obtained, 1 four molecules asymmetric unit 2...
Abstract The structure of the trigonal crystal form bovine β‐lactoglobulin variant B at pH 7.1 has been determined by X‐ray diffraction methods a resolution 2.22 Å and refined to values for R free 0.239 0.286, respectively. By comparison with A 7.1, which was previously [Qin BY et al., 1998, Biochemistry 37 :14014—14023], structural consequences sequence differences D64G V118A variants B, respectively, have investigated. Only minor in core calyx occur. In vicinity mutation site on loop CD...
ABSTRACT The extracellular region of the coxsackievirus and adenovirus receptor (CAR) is predicted to consist two immunoglobulin (Ig)-related structural domains. We expressed isolated CAR amino-terminal domain (D1) a fragment containing both Ig domains (D1/D2) in Escherichia coli . Both D1 D1/D2 formed complexes vitro with recombinant knob type 12 (Ad12) fiber, inhibited 2 (Ad2) infection HeLa cells. These results indicate that adenovirus-binding activity localized IgV-related confirm our...
The molecular function of occludin, an integral membrane component tight junctions, remains unclear. VEGF-induced phosphorylation sites were mapped on occludin by combining MS data analysis with bioinformatics. In vivo Ser490 was validated and protein interaction studies combined crystal structure suggest that attenuates the between ZO-1. This study demonstrates bioinformatics can successfully identify novel from limiting samples.
Retroviral Gag polyproteins coopt host factors to traffic from cytosolic ribosomes the plasma membrane, where virions are released. Before membrane transport, multidomain protein of Rous sarcoma virus (RSV) undergoes importin-mediated nuclear import and CRM1-dependent export, an intrinsic step in assembly pathway. Transient trafficking is required for efficient viral RNA (vRNA) encapsidation, suggesting that Gag:vRNA binding might occur nucleus. Here, we show imported into nucleus through...
Autophagosome formation, a crucial step in macroautophagy (autophagy), requires the covalent conjugation of LC3 proteins to amino headgroup phosphatidylethanolamine (PE) lipids. Atg3, an E2-like enzyme, catalyzes transfer from LC3-Atg3 PEs targeted membranes. Here we show that catalytically important C-terminal regions human Atg3 (hAtg3) are conformationally dynamic and directly interact with membrane, collaboration its N-terminal membrane curvature-sensitive helix. The functional relevance...
Tight junctions (TJs) are dynamic cellular structures that critical for compartmentalizing environments within tissues and regulating transport of small molecules, ions, fluids. Phosphorylation-dependent binding the transmembrane protein occludin to structural organizing ZO-1 contributes regulation barrier properties; however, details their interaction controversial. Using angle X-ray scattering (SAXS), NMR chemical shift perturbation, cross-saturation, in vitro binding, site-directed...
Abstract VPS37A, an ESCRT-I complex component, is required for recruiting a subset of ESCRT proteins to the phagophore autophagosome closure. However, mechanism by which VPS37A targeted remains obscure. Here, we demonstrate that N-terminal domain exhibits selective interactions with highly curved membranes, mediated two membrane-interacting motifs within disordered regions surrounding its Ubiquitin E2 variant-like (UEVL) domain. Site-directed mutations residues in these disrupt localization...
Cytochrome b5 reductase (cb5r) (EC 1.6.6.2) catalyzes the reduction of two molecules cytochrome using NADH as physiological electron donor. The structure pig cb5r at 2.4 Å resolution was previously reported in literature, but it inconsistent with biochemistry; for example, K83 and C245 were both implicated mechanism, not located active site. To address this problem, we have determined structures from rat 2.0 a complex NAD+ 2.3 resolution. We found significant differences throughout compared...
Spermidine/spermine N 1 -acetyltransferase (SSAT) is a key enzyme in the control of polyamine levels human cells, as acetylation spermidine and spermine triggers export or degradation. Increased intracellular accompany several types cancers well other diseases, compounds that affect expression, activity, stability SSAT are being explored potential therapeutic drugs. We have expressed from cloned cDNA Escherichia coli determined high-resolution structures wild-type mutant SSAT, free dimer...
Abstract The Saccharomyces cerevisiae Gal80 protein has two binding partners: Gal4 and Gal3. In the absence of galactose, binds to inhibits transcriptional activation domain (AD) GAL gene activator, Gal4, preventing expression. Galactose triggers an association between Gal3 Gal80, relieving inhibition Gal4. We selected for GAL80 mutants with impaired capacity bind or Gal4AD. Most variants Gal4AD retained their self-associate, whereas most those lost ability self-associate. Thus, some amino...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of chicken annexin V at 2.25-.ANG. resolutionMaria C. Bewley, Catherine M. Boustead, John H. Walker, David A. Waller, and Robert HuberCite this: Biochemistry 1993, 32, 15, 3923–3929Publication Date (Print):April 20, 1993Publication History Published online1 May 2002Published inissue 20 April 1993https://pubs.acs.org/doi/10.1021/bi00066a011https://doi.org/10.1021/bi00066a011research-articleACS PublicationsRequest reuse permissionsArticle...
PRINTS is a compendium of protein motif fingerprints derived from the OWL composite sequence database. Fingerprints are groups motifs within alignments whose conserved nature allows them to be used as signatures family membership. inherently offer improved diagnostic reliability over single methods by virtue mutual context provided neighbors. To date, 650 have been constructed and stored in PRINTS, size which has doubled last 2 years. The current version, 14.0, encodes 3500 motifs, covering...
Abstract Most known chemopreventive agents including certain selenium compounds suppress the activation of nuclear factor κB (NF-κB), but mechanisms remain largely elusive. Toward this end, we initially showed that inhibition NF-κB DNA binding by benzyl selenocyanate (BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) was reversed addition DTT; suggests formation DTT-reducible selenium-sulfur bonds between moieties cysteine residues in (p50) protein. Furthermore, inhibitory effect...