257 research outputs found
Partial Transmutation of Singularities in Optical Instruments
Some interesting optical instruments such as the Eaton lens and the Invisible
Sphere require singularities of the refractive index for their implementation.
We show how to transmute those singularities into harmless topological defects
in anisotropic media without the need for anomalous material properties
Multidimensional NMR identifies the conformational shift essential for catalytic competence in the 60-kDa Drosophila melanogaster dUTPase trimer
The catalytic mechanism of dUTP pyrophosphatase (dUTPase), responsible
for the prevention of uracil incorporation into DNA, involves ordering
of the flexible C terminus of the enzyme. This conformational shift is
investigated by multidimensional NMR on the Drosophila enzyme. Flexible
segments of the homotrimer give rise to sharp resonances in the
H-1-N-15 heteronuclear single-quantum coherence (HSQC) spectra, which
are clearly distinguishable from the background resonances of the well
folded protein globule. Binding of the product dUMP or the analogues
dUDP and alpha,beta-imino-dUTP to the enzyme induces a conformational
change reflected in the disappearance of eight sharp resonances. This
phenomenon is interpreted as nucleotide binding-induced ordering of
some residues upon the folded protein globule. Three-dimensional
N-15-edited H-1-N-15 HSQC total correlation spectroscopy (TOCSY) and
H-1-N-15 HSQC nuclear Overhauser effect spectroscopy measurements
allowed clear assignment of these eight specific resonance peaks. The
residues identified correspond to the conserved C-terminal sequence
motif, indicating that (i) this conformational shift is amenable to NMR
studies in solution even in the large trimeric molecule and (ii)
formation of the closed enzyme conformer in the case of the Drosophila
enzyme does not require the complete triphosphate chain of the
substrate. NMR titration of the enzyme with the nucleotide ligands as
well as kinetic data indicated significant deviation from the model of
independent active sites within the homotrimer. The results suggest
allosterism in the eukaryotic dUTPase
The mechanism of the reverse recovery-step, phosphate release, and actin activation of Dictyostelium myosin II.
The rate-limiting step of the myosin basal ATPase (i.e. in absence of actin) is assumed to be a post-hydrolysis swinging of the lever arm (reverse recovery step), that limits the subsequent rapid product release steps. However, direct experimental evidence for this assignment is lacking. To investigate the binding and the release of ADP and phosphate independently from the lever arm motion, two single tryptophan-containing motor domains of Dictyostelium myosin II were used. The single tryptophans of the W129+ and W501+ constructs are located at the entrance of the nucleotide binding pocket and near the lever arm, respectively. Kinetic experiments show that the rate-limiting step in the basal ATPase cycle is indeed the reverse recovery step, which is a slow equilibrium step (k(forward) = 0.05 s(-1), k(reverse) = 0.15 s(-1)) that precedes the phosphate release step. Actin directly activates the reverse recovery step, which becomes practically irreversible in the actin-bound form, triggering the power stroke. Even at low actin concentrations the power stroke occurs in the actin-attached states despite the low actin affinity of myosin in the pre-power stroke conformation
Cloaking and imaging at the same time
In this letter, we propose a conceptual device to perform subwavelength
imaging with positive refraction. The key to this proposal is that a drain is
no longer a must for some cases. What's more, this device is an isotropic
omnidirectional cloak with a perfect electric conductor hiding region and shows
versatile illusion optical effects. Numerical simulations are performed to
verify the functionalities.Comment: 15 pages, 4 figure
The structure of the complex of calmodulin with KAR-2: a novel mode of binding explains the unique pharmacology of the drug
3'-(beta-
Chloroethyl)-2',4'-dioxo-3,5'-spiro-oxazolidino-4-deacetoxyvinblastine
(KAR-2) is a potent anti-microtubular agent that arrests mitosis in
cancer cells without significant toxic side effects. In this study we
demonstrate that in addition to targeting microtubules, KAR-2 also
binds calmodulin, thereby countering the antagonistic effects of
trifluoperazine. To determine the basis of both properties of KAR-2,
the three-dimensional structure of its complex with Ca2+-calmodulin has
been characterized both in solution using NMR and when crystallized
using x-ray diffraction. Heterocorrelation (H-1-N-15 heteronuclear
single quantum coherence) spectra of N-15-labeled calmodulin indicate a
global conformation change (closure) of the protein upon its binding to
KAR-2. The crystal structure at 2.12-Angstrom resolution reveals a more
complete picture; KAR-2 binds to a novel structure created by amino
acid residues of both the N- and C- terminal domains of calmodulin.
Although first detected by x-ray diffraction of the crystallized
ternary complex, this conformational change is consistent with its
solution structure as characterized by NMR spectroscopy. It is
noteworthy that a similar tertiary complex forms when calmodulin binds
KAR-2 as when it binds trifluoperazine, even though the two ligands
contact (for the most part) different amino acid residues. These
observations explain the specificity of KAR-2 as an anti-microtubular
agent; the drug interacts with a novel drug binding domain on
calmodulin. Consequently, KAR-2 does not prevent calmodulin from
binding most of its physiological targets
Can NO2+ exist in bent or cyclic forms?
Calculations of NO2+ at HF, CBS-4, CASSCF, MBPT(2), MBPT(3), and
MBPT(4) theory levels, using 3-21G and 6-31G(d) basis sets, found two
C-2V structures along with the linear geometry. Computations using
MBPT(2) and CCSD(T) approaches and the aug-cc-pvtz basis set confirmed
these results. Harmonic vibrational frequency calculations, performed
with MBPT(2) and CCSD(T) theories, indicated that the linear structure
was the global minimum while one of the bent structures (angle ONO = 80
degrees) was a higher energy local minimum. The second C-2V structure
(angle ONO = 45 degrees) exhibited a large imaginary vibrational
frequency along the asymmetric stretching (B-2) mode, indicating its
saddle point nature. (C) 2001 Elsevier Science B.V. All rights reserved
Penetratin and Derivatives Acting as Antibacterial Agents
The synthesis, in vitro evaluation and conformational study of penetratin and structurally related derivatives acting as antibacterial agents are reported. Among the compounds evaluated here, two methionine sulphoxide derivatives (RQIKIWFQNRRM[O]KWKK-NH2 and RQIKIFFQNRRM[O]KFKK-NH2) exhibited the strongest antibacterial effect in this series. In order to better understand the antimicrobial activity obtained for these peptides, we performed an exhaustive conformational analysis using different approaches. Molecular dynamics simulations were performed using two different media (water and trifluoroethanol/water). The results of these theoretical calculations were corroborated using experimental CD measurements. The electronic study for these peptides was carried out using molecular electrostatic potentials obtained from RHF/6-31G(d) calculations. In addition, the non-apeptide RQIRRWWQR-NH2 showed strong inhibitory action against the Gram-negative and Gram-positive bacteria tested in this study
Peptide Models - XXIV: An ab Initio Study on N-formyl-l-prolinamide With Trans Peptide Bond. The Existence or Non-existence of Alpha(l) And Epsilon(l) Conformations
N-formyl-L-prolinamide was subjected to geometry optimization at three levels of theory: HF/3-21G, HF/6-31G (d) and B3LYP/6-31G (d). At all three levels of computation the global minimum was gamma(L) (inverse gamma-Turn) backbone conformation with two ring-puckered forms "UP" and "DOWN". At HF/3-21G level of theory three backbone conformations were found gamma(L), epsilon(L), and alpha(L). At higher levels of theory the epsilon(L), and alpha(L) conformations disappeared. The ''UP'' and ''DOWN'' ring-puckered forms, in the gamma(L) backbone conformation, led to practically identical vibrational spectra at the B3LYP/6-31G (d) level of theory
Prospects in computational molecular medicine: a millennial mega-project on peptide folding
During the second half of the 20th century, Molecular Computations have
reached to a level that can revolutionize chemistry. The next target
will be structural biology, which will be followed soon by Molecular
Medicine. The present paper outlines where we are at, in this field, at
the end of the 20th century, and in what direction the development may
take in the new millennium. In view of the gigantic nature of the
problem, it is suggested that a suitably designed cooperative
Millennial Mega-project might accelerate our schedule. (C) 2000
Elsevier Science B.V. All rights reserved
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