56 research outputs found
Species-Specific and Inhibitor-Dependent Conformations of LpxC: Implications for Antibiotic Design
LpxC is an essential enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different Gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against Gram-negative infections
Carbohyrate Analysis:Â High Performance Liquid Chromatography and Capillary Electrophoresis Edited by Ziad El Rassi (Oklahoma State University). Elsevier:Â Amsterdam. 1995. xix + 668 pp. $242.75. ISBN 0-444-89981-2.
Multivalency Effects in ProteinâCarbohydrate Interaction:Â The Binding of the Shiga-like Toxin 1 Binding Subunit to Multivalent C-
Microcalorimetric Determination of Thermodynamic Parameters for IonophoreâSiderophore HostâGuest Complex Formation
Additivity and the Physical Basis of Multivalency Effects:Â A Thermodynamic Investigation of the Calcium EDTA Interaction
Specific Binding at the Cellulose Binding ModuleâCellulose Interface Observed by Force Spectroscopy
The need for effective enzymatic
depolymerization of cellulose
has stimulated an interest in interactions between protein and cellulose.
Techniques utilized for quantitative measurements of proteinâcellulose
noncovalent association include microgravimetry, calorimetry, and
atomic force microscopy (AFM), none of which differentiate between
specific proteinâcellulose binding and nonspecific adhesion.
Here, we describe an AFM approach that differentiates nonspecific
from specific interactions between cellulose-binding modules (CBMs)
and cellulose. We demonstrate that the âmismatchedâ
interaction between murine galectin-3, a lectin with no known affinity
for cellulose, and cellulose shows molecular recognition force microscopy
profiles similar to those observed during the interaction of a âmatchedâ
clostridial CBM3a with the same substrate. We also examine differences
in binding probabilities and rupture profiles during CBMâcellulose
binding experiments in the presence and absence of a blocking agentî¸a
substrate specific for CBM that presumably blocks binding sites. By
comparison of the behavior of the two proteins, we separate specific
(i.e., blockable) and nonspecific adhesion events and show that both
classes of interaction exhibit nearly identical rupture forces (45
pN at âź0.4 nN/s). Our work provides an important caveat for
the interpretation of proteinâcarbohydrate binding by force
spectroscopy; delineation of the importance of such interactions to
other classes of binding warrants further study
2-Keto-3-deoxy-6-phosphogalactonate Aldolase as a Catalyst for Stereocontrolled CarbonâCarbon Bond Formation
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