Abstract：
:Molecular dynamics simulations of protein tyrosine phosphatase 1B (PTP1B) complexed with the phosphorylated peptide substrate DADEpYL and the free substrate have been conducted to investigate 1) the physical forces involved in substrate-protein interactions, 2) the importance of enzyme and substrate flexibility for binding, 3) the electrostatic properties of the enzyme, and 4) the contribution from solvation. The simulations were performed for 1 ns, using explicit water molecules. The last 700 ps of the trajectories was used for analysis determining enthalpic and entropic contributions to substrate binding. Based on essential dynamics analysis of the PTP1B/DADEpYL trajectory, it is shown that internal motions in the binding pocket occur in a subspace of only a few degrees of freedom. In particular, relatively large flexibilities are observed along several eigenvectors in the segments: Arg(24)-Ser(28), Pro(38)-Arg(47), and Glu(115)-Gly(117). These motions are correlated to the C- and N-terminal motions of the substrate. Relatively small fluctuations are observed in the region of the consensus active site motif (H/V)CX(5)R(S/T) and in the region of the WPD loop, which contains the general acid for catalysis. Analysis of the individual enzyme-substrate interaction energies revealed that mainly electrostatic forces contribute to binding. Indeed, calculation of the electrostatic field of the enzyme reveals that only the field surrounding the binding pocket is positive, while the remaining protein surface is characterized by a predominantly negative electrostatic field. This positive electrostatic field attracts negatively charged substrates and could explain the experimentally observed preference of PTP1B for negatively charged substrates like the DADEpYL peptide.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Peters GH,Frimurer TM,Andersen JN,Olsen OHdoi
10.1016/S0006-3495(00)76768-3subject
Has Abstractpub_date
2000-05-01 00:00:00pages
2191-200issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(00)76768-3journal_volume
78pub_type
杂志文章abstract：:The properties of phosphatidylcholines (PCs) having a perdeuterated stearic acid, 18:0d35, in the sn-1 position and the fatty acid 18:0, 18:1 omega 9, 18:2 omega 6, 18:3 omega 3, 20:4 omega 6, 20:5 omega 3, or 22:6 omega 3 at the sn-2 position were investigated in a matrix of dioleoylphosphatidylethanolamine (DOPE) by...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(96)79223-8
更新日期：1996-07-01 00:00:00
abstract：:N-methyl-d-aspartate (NMDA) receptors are glutamate- and glycine-gated channels that flux Na+ and Ca2+ into postsynaptic neurons during synaptic transmission. The resulting intracellular Ca2+ transient is essential to physiological and pathological processes related to synaptic development, plasticity, and apoptosis. ...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2017.06.035
更新日期：2017-11-21 00:00:00
abstract：:Fluorescence correlation microscopy (FCM), the combination of fluorescence correlation spectroscopy (FCS) and digital microscopy (Brock and Jovin, 1998. Cell. Mol. Biol. 44:847-856), has been implemented for measuring molecular diffusion and association in living cells with explicit consideration of autocorrelations a...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(98)77699-4
更新日期：1998-11-01 00:00:00
abstract：:Biological membranes are composed of a large number lipid species differing in hydrophobic length, degree of saturation, and charge and size of the headgroup. We now present data on the effect of hydrocarbon chain length of the lipids and headgroup composition on the lateral mobility of the proteins in model membranes...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2010.06.036
更新日期：2010-09-08 00:00:00
abstract：:The pathway to membrane fusion in synthetic and biological systems is thought to pass through hemifusion, in which the outer leaflets are fused while the inner leaflets engage in a hemifusion diaphragm (HD). Fusion has been proposed to be completed by lysis of the expanded HD that matures from a localized stalklike in...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2012.06.041
更新日期：2012-08-22 00:00:00
abstract：:Nuclear transport receptors (NTRs) mediate nucleocytoplasmic transport via their affinity for unstructured proteins (polymers) in the nuclear pore complex (NPC). Here, we have modeled the effect of NTRs on polymeric structure in the nanopore confinement of the NPC central conduit. The model explicitly takes into accou...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2013.11.013
更新日期：2013-12-17 00:00:00
abstract：:We have studied the combined effects of X-irradiation and nitrogen mustard treatment on the colony-forming ability of Chinese hamster cells. In contrast to X-irradiation, nitrogen mustard acting by itself yields an exponential dose-effect relationship. Moreover, whether delivered in immediate sequence or after varying...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(69)86439-8
更新日期：1969-09-01 00:00:00
abstract：:The electric quadrupole moment of the deuterium nucleus provides a nuclear magnetic resonance (NMR) probe of electric field gradients, and thereby of organization of tissue water. 8-17% of H(2)O in rat muscle and brain was replaced by D(2)O from 50% deuterated drinking water. The peak height of the steady-state NMR sp...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(69)86388-5
更新日期：1969-03-01 00:00:00
abstract：:A 15-ns molecular dynamics (MD) simulation of the fully hydrated dimyristoylphosphatidylcholine-cholesterol (DMPC-Chol) bilayer in the liquid-crystalline state was carried out to investigate the effect of Chol on the hydrocarbon chain region of the bilayer. The last 8-ns fragment of the generated trajectory was used f...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(01)75867-5
更新日期：2001-10-01 00:00:00
abstract：:Cell/matrix adhesions are modulated by cytoskeletal or external stresses and adapt to the mechanical properties of the extracellular matrix. We propose that this mechanosensitivity arises from the activation of a mechanosensor located within the adhesion itself. We show that this mechanism accounts for the observed di...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1529/biophysj.105.077115
更新日期：2006-07-01 00:00:00
abstract：:A new Fourier series representation of supercoiled DNA is employed in Langevin dynamics simulations to study large-scale configurational motions of intermediate-length chains. The polymer is modeled as an ideal elastic rod subject to long-range van der Waals' interactions. The van der Waals' term prevents the self-con...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(97)78205-5
更新日期：1997-10-01 00:00:00
abstract：:With a view to determine the configuration and regularity of plectonemically supercoiled DNA, we have measured the small angle neutron scattering from pUC18 plasmid in saline solutions. Furthermore, we have derived the mathematical expression for the single chain scattering function (form factor) of a superhelical str...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(02)75234-X
更新日期：2002-08-01 00:00:00
abstract：:The physical characteristics which govern the water relations of the giant-celled sporangiophore of Phycomyces blakesleeanus were measured with the pressure probe technique and with nanoliter osmometry. These properties are important because they govern water uptake associated with cell growth and because they may in...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(87)83363-5
更新日期：1987-03-01 00:00:00
abstract：:Stationary and nonstationary correlation-frequency analysis of heterodyne laser light scattering were utilized to make automated, on-line, objective measurements of tracheal ciliary beat frequency (CBF) in intact, anesthetized canines. The stationary correlation-frequency analysis laser light-scattering technique was ...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/s0006-3495(94)80864-1
更新日期：1994-03-01 00:00:00
abstract：:Biophysical understanding of membrane domains requires accurate knowledge of their structural details and elasticity. We report on a global small angle x-ray scattering data analysis technique for coexisting liquid-ordered (Lo) and liquid-disordered (Ld) domains in fully hydrated multilamellar vesicles. This enabled t...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2014.11.3488
更新日期：2015-02-17 00:00:00
abstract：:Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1529/biophysj.108.134155
更新日期：2008-11-01 00:00:00
abstract：:The single photon response in vertebrate phototransduction is highly reproducible despite a number of random components of the activation cascade, including the random activation site, the random walk of an activated receptor, and its quenching in a random number of steps. Here we use a previously generated and tested...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1529/biophysj.107.114058
更新日期：2008-05-01 00:00:00
abstract：:Very high dielectric constants have been observed for bacteria at low frequencies. High dielectric constants such as these can be explained by a theory which has been developed for the low-frequency dielectric dispersion of porous charged particles and which has been tested successfully through measurements with ion e...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(73)85966-1
更新日期：1973-01-01 00:00:00
abstract：:The diffusion of plastoquinol and its binding to the cytochrome bf complex, which occurs during linear photosynthetic electron transport and is analogous to reaction sequences found in most energy-converting membranes, has been studied in intact thylakoid membranes. The flash-induced electron transfer between the late...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(90)82445-0
更新日期：1990-10-01 00:00:00
abstract：:The general formalism required to treat two-state sliding filament models of muscle contraction, including free energy considerations, is first reviewed and amplified. This formalism is then used to examine, and modify as needed, three models studied previously by Podolsky and Nolan, in which cross-bridge attachment-d...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(75)85823-1
更新日期：1975-04-01 00:00:00
abstract：:Cytoplasmic free Mg(2+) concentration ([Mg(2+)]i) was measured in rat ventricular myocytes with a fluorescent indicator furaptra (mag-fura-2) introduced by AM-loading. By incubation of the cells in a high-K(+) (Ca(2+)- and Mg(2+)-free) solution, [Mg(2+)]i decreased from ? 0.9 mM to 0.2 to 0.5 mM. The lowered [Mg(2+)]i...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2014.09.015
更新日期：2014-11-04 00:00:00
abstract：:Cryoelectron microscopy has been used to study the reorganization of unilamellar cationic lipid vesicles upon the addition of DNA. Unilamellar DNA-coated vesicles, as well as multilamellar DNA lipid complexes, could be observed. Also, DNA induced fusion of unilamellar vesicles was found. DNA appears to adsorb to the o...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(99)77467-9
更新日期：1999-06-01 00:00:00
abstract：:Gigaohm recordings have been made from glutamate receptor channels in excised, outside-out patches of collagenase-treated locust muscle membrane. The channels in the excised patches exhibit the kinetic state switching first seen in megaohm recordings from intact muscle fibers. Analysis of channel dwell time distributi...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(90)82367-5
更新日期：1990-07-01 00:00:00
abstract：:Intrinsically disordered proteins play important roles throughout biology, yet our understanding of the relationship between their sequences, structural properties, and functions remains incomplete. The dynamic nature of these proteins, however, makes them difficult to characterize structurally. Many disordered protei...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/j.bpj.2017.06.042
更新日期：2017-08-08 00:00:00
abstract：:The biophysical properties and cellular distribution of ion channels largely determine the input/output relationships of electrically excitable cells. A variety of patch pipette voltage clamp techniques are available to characterize ionic currents. However, when used by themselves, such techniques are not well suited ...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(98)78003-8
更新日期：1998-06-01 00:00:00
abstract：:We have used resonance Raman spectroscopy to probe the heme environment of a recently discovered NOS from the pathogenic bacterium Staphylococcus aureus, named SANOS. We detect two forms of the CO complex in the absence of L-arginine, with nu(Fe-CO) at 482 and 497 cm(-1) and nu(C-O) at 1949 and 1930 cm(-1), respective...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1529/biophysj.104.042119
更新日期：2004-09-01 00:00:00
abstract：:We present here an efficient and accurate procedure for modeling of the three-dimensional structures of polypeptides in the explicit solvent water based on molecular dynamics calculations. Using the toxic domain analog of heat-stable enterotoxin as a model peptide, we examined the utilities of two molecular dynamics t...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(94)80975-0
更新日期：1994-06-01 00:00:00
abstract：:Here we present a model for maltodextrin translocation through maltoporin channels. In a first step, our theoretical analysis does consider the case of a single binding site for a given substrate in a structurally unaffected channel with a possibly different entrance barrier on either side. It is shown how by means of...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(03)70025-3
更新日期：2003-05-01 00:00:00
abstract：:Structure factor amplitudes and phases can be computed directly from electron cryomicroscopy images. Inherent aberrations of the electromagnetic lenses and other instrumental factors affect the structure factors, however, resulting in decreased accuracy in the determined three-dimensional reconstruction. In contrast, ...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1016/S0006-3495(99)77381-9
更新日期：1999-04-01 00:00:00
abstract：:We developed a model of the rat ventricular myocyte at room temperature to predict the relative effects of different mechanisms on the cause of the slow increase in force in response to a step change in muscle length. We performed simulations in the presence of stretch-dependent increases in flux through the Na(+)-H(+...
journal_title：Biophysical journal
pub_type： 杂志文章
doi：10.1529/biophysj.106.095463
更新日期：2007-06-01 00:00:00
