The role of enzyme distortion in the single displacement mechanism of family 19 chitinases

By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′ N-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed.

Compression, gain, and nonlinear distortion in an active cochlear model with subpartitions

The propagation of inhomogeneous, weakly nonlinear waves is considered in a cochlear model having two degrees of freedom that represent the transverse motions of the tectorial and basilar membranes within the organ of Corti. It is assumed that nonlinearity arises from the saturation of outer hair cell active force generation. I use multiple scale asymptotics and treat nonlinearity as a correction to a linear hydroelastic wave. The resulting theory is used to explain experimentally observed features of the response of the cochlear partition to a pure tone, including: the amplification of the response in a healthy cochlea vs a dead one; the less than linear growth rate of the response to increasing sound pressure level; and the amount of distortion to be expected at high and low frequencies at basal and apical locations, respectively. I also show that the outer hair cell nonlinearity generates retrograde waves.

Geometric constraints explain much of the species richness pattern in African birds

The world contains boundaries (e.g., continental edge for terrestrial taxa) that impose geometric constraints on the distribution of species ranges. Thus, contrary to traditional thinking, the expected species richness pattern in absence of ecological or physiographical factors is unlikely to be uniform. Species richness has been shown to peak in the middle of a bounded one-dimensional domain, even in the absence of ecological or physiographical factors. Because species ranges are not linear, an extension of the approach to two dimensions is necessary. Here we present a two-dimensional null model accounting for effects of geometric constraints. We use the model to examine the effects of continental edge on the distribution of terrestrial animals in Africa and compare the predictions with the observed pattern of species richness in birds endemic to the continent. Latitudinal, longitudinal, and two-dimensional patterns of species richness are predicted well from the modeled null effects alone. As expected, null effects are of high significance for wide ranging species only. Our results highlight the conceptual significance of an until recently neglected constraint from continental shape alone and support a more cautious analysis of species richness patterns at this scale.

Distortion in the spacer region of Pm during activation of middle transcription of phage Mu.

Transcription from the middle promoter, Pm, of phage Mu is initiated by Escherichia coli RNA polymerase holoenzyme (E sigma 70; RNAP) and the phage-encoded activator, Mor. Point mutations in the spacer region between the -10 hexamer and the Mor binding site result in changes of promoter activity in vivo. These mutations are located at the junction between a rigid T-tract and adjacent, potentially deformable G + C-rich DNA segment, suggesting that deformation of the spacer region may play a role in the transcriptional activation of Pm. This prediction was tested by using dimethyl sulfate and potassium permanganate footprinting analyses. Helical distortion involving strand separation was detected at positions -32 to -34, close to the predicted interface between Mor and RNAP. Promoter mutants in which this distortion was not detected exhibited a lack of melting in the -12 to -1 region and reduced promoter activity in vivo. We propose that complexes containing the distortion represent stressed intermediates rather than stable open complexes and thus can be envisaged as a transition state in the kinetic pathway of Pm activation in which stored torsional energy could be used to facilitate melting around the transcription start point.

Geometric incompatibility in a fault system.

Interdependence between geometry of a fault system, its kinematics, and seismicity is investigated. Quantitative measure is introduced for inconsistency between a fixed configuration of faults and the slip rates on each fault. This measure, named geometric incompatibility (G), depicts summarily the instability near the fault junctions: their divergence or convergence ("unlocking" or "locking up") and accumulation of stress and deformations. Accordingly, the changes in G are connected with dynamics of seismicity. Apart from geometric incompatibility, we consider deviation K from well-known Saint Venant condition of kinematic compatibility. This deviation depicts summarily unaccounted stress and strain accumulation in the region and/or internal inconsistencies in a reconstruction of block- and fault system (its geometry and movements). The estimates of G and K provide a useful tool for bringing together the data on different types of movement in a fault system. An analog of Stokes formula is found that allows determination of the total values of G and K in a region from the data on its boundary. The phenomenon of geometric incompatibility implies that nucleation of strong earthquakes is to large extent controlled by processes near fault junctions. The junctions that have been locked up may act as transient asperities, and unlocked junctions may act as transient weakest links. Tentative estimates of K and G are made for each end of the Big Bend of the San Andreas fault system in Southern California. Recent strong earthquakes Landers (1992, M = 7.3) and Northridge (1994, M = 6.7) both reduced K but had opposite impact on G: Landers unlocked the area, whereas Northridge locked it up again.