A5090313113- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Lipid Membrane Structure and Behavior
- Clostridium difficile and Clostridium perfringens research
- Nanopore and Nanochannel Transport Studies
- Cardiac electrophysiology and arrhythmias
- Neurobiology and Insect Physiology Research
- Cephalopods and Marine Biology
- RNA and protein synthesis mechanisms
- Yersinia bacterium, plague, ectoparasites research
- Toxin Mechanisms and Immunotoxins
- Protein Structure and Dynamics
- Olfactory and Sensory Function Studies
- Force Microscopy Techniques and Applications
- thermodynamics and calorimetric analyses
- Venomous Animal Envenomation and Studies
- Thermoregulation and physiological responses
- Bacterial Genetics and Biotechnology
- Neural dynamics and brain function
- Antibiotic Resistance in Bacteria
- Diet and metabolism studies
- Neuroscience and Neuropharmacology Research
- Connexins and lens biology
- Curcumin's Biomedical Applications
- Neuroendocrine regulation and behavior
The University of Texas Southwestern Medical Center
2012-2022
Southwestern Medical Center
2010-2021
Texas Medical Center
2013
Fundación Ciencias Exactas y Naturales
2004-2005
University of Buenos Aires
1999-2005
Mechanosensitive (MS) channels are universal cellular membrane pores. Bacterial MS channels, as typified by channel of small conductance (MscS) from Escherichia coli ( Ec MscS), release osmolytes under hypoosmotic conditions. known to be ion selective different extents, but the underlying mechanism remains poorly understood. Here we identify an anion-selective MscS Thermoanaerobacter tengcongensis Tt MscS). The structure closely resembles that MscS, it lacks large cytoplasmic equatorial...
The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery declining, with most the recently approved antibiotics corresponding uses for old or structurally similar derivatives known antibiotics. We used an in silico approach design class nontoxic antimicrobials bacteria-specific mechanosensitive ion channel large conductance, MscL. One antimicrobial this class, compound 10, effective against methicillin-resistant...
The primary mechanism of action the antibiotic dihydrostreptomycin is binding to and modifying function bacterial ribosome, thus leading decreased aberrant translation proteins; however, routes by which it enters cell are largely unknown. mechanosensitive channel large conductance, MscL, found in vast majority species, where serves as an emergency release valve rescuing from sudden decreases external osmolarity. While known that MscL expression increases potency dihydrostreptomycin, has...
The mechanosensitive channel of large conductance, MscL, has been proposed as a triggered nanovalve to be used in drug release and other nanodevices. It is small homopentameric bacterial protein that the largest gated pore known: greater than 30 Å. Large molecules, even proteins can released through MscL. Although MscL normally gates response membrane tension, early studies found hydrophilic or charged residue substitutions near constriction leads opening. Researchers have successfully...
The mechanosensitive channel of large conductance (MscL) from E. coli serves as an emergency release valve allowing the cell to survive acute osmotic downshock. It is one best studied channels and a paradigm for how protein can sense respond membrane tension. Two MscL crystal structures orthologs M. tuberculosis S. aureus have been solved showing pentameric tetrameric structures, respectively. Several studies followed understand whether discrepancy in their stoichiometry was species...
Mechanosensitive channels are present in all living organisms and thought to underlie the senses of touch hearing as well various important physiological functions like osmoregulation vasoregulation. The mechanosensitive channel large conductance (MscL) from Escherichia coli was first protein shown encode activity serves a paradigm for how responds mechanical stimuli. MscL plays role osmoprotection E. coli, acting an emergency release valve that is activated by membrane tension due cell...
The bacterial MscL channel normally functions as an emergency release valve discharging cytoplasmic solutes upon osmotic stress. opens and passes molecules up to 30 Å its pore is the largest of any gated channel. Opening inappropriately detrimental cell, suggesting a potential novel drug target. A small-molecule compound, 011A, has been shown increase sensitivity Escherichia coli channel, slow growth, even decrease viability quiescent cultures. mscL gene highly conserved found in vast...
The antibiotic resistance crisis is becoming dire, yet in the past several years few potential antibiotics or adjuvants with novel modes of action have been identified. bacterial mechanosensitive channel large conductance, MscL, found majority species, including pathogens, normally functions as an emergency release valve, sensing membrane tension upon low-osmotic stress and discharging cytoplasmic solutes before cell lysis. Opening huge ~30Å diameter pore MscL inappropriately detrimental to...
The bacterial mechanosensitive channel MscL is the best-studied mechanosensor, thus serving as a paradigm of how protein senses and responds to mechanical force. Models for transition Escherichia coli from closed open states propose tilting transmembrane domains in plane membrane, suggesting dynamic protein-lipid interactions. Here, we used rapid vivo assay assess function channels that were post-translationally modified at several different sites region just distal cytoplasmic end second...
The bacterial mechanosensitive channel of large conductance (MscL) normally functions as an emergency release valve discharging cytoplasmic solutes upon osmotic stress. Opening the pore MscL inappropriately is detrimental to cell, and thus it has been speculated be a potential antibiotic target. Although one best studied channels, no chemical that influenced growth by modulating known. We therefore used high-throughput screen identify compounds slowed in MscL-dependent manner. characterized...
Curcumin, a natural compound isolated from the rhizome of turmeric, has been shown to have antibacterial properties. It several physiological effects on bacteria including an apoptosis-like response involving RecA, membrane permeabilization, inhibiting septation, and it can also work synergistically with other antibiotics. The mechanism by which curcumin permeabilizes bacterial unclear. Most species contain Mechanosensitive channel large conductance, MscL, serves function biological...
Resistance to antibiotics is a serious and worsening threat human health worldwide, there an urgent need develop new that can avert it. One possible solution the development of compounds possess multiple modes action, requiring at least two mutations acquire resistance. Compound SCH-79797 both avoids resistance has mechanisms action: one inhibiting folate pathway, second described as "membrane permeabilization"; however, mechanism by which membranes from bacterial cells, but not host, are...
The bacterial mechanosensitive channel of large conductance, MscL, is one the best characterized channels serving as a paradigm for how proteins can sense and transduce mechanical forces. physiological role MscL that an emergency release valve opens pore upon sudden drop in osmolarity environment. A crystal structure closed state shows it homopentamer, with each subunit consisting two transmembrane domains (TM). There consensus TM helices move iris like manner tilting plane membrane while...
Serotonin [5-hydroxytryptamine (5-HT)] is a conspicuous neuromodulator of sensory-motor networks that affects variety neurons at different levels the network hierarchy. Because its many possible targets, it has been difficult to obtain comprehensive picture how 5-HT achieves final modulatory output on any given network. Our hypothesis profile actions dictated by pattern release from endogenous sites. We tested this in leech nervous system means selective serotonin reuptake blocker (SSRI),...
MscL is a highly conserved mechanosensitive channel found in the majority of bacterial species, including pathogens. It functions as biological emergency release valve, jettisoning solutes from cytoplasm upon acute hypoosmotic stress. opens largest known gated pore and has been heralded an antibacterial target. Although there are no endogenous ligands, small compounds have recently shown to specifically bind open channel, leading decreased cell growth viability. Their binding site at...