Substrate entering and product leaving trajectories predict an engulfing dynamic for the major conformational change of the β-lactam acylase

It is still a major challenge to acquire insight into the conformational changes between the ground state and the transition state of an enzyme, although conformational fluctuation within interconverting conformers has been widely investigated (1-4). Here, we utilize different enzymatic reactions in b-lactam acylase to figure out the substrate/product trajectories in the enzyme, thereby probing the overall conformational changes in transition state. First, an auto-proteolytic intermediate of cephalosporin acylase (EC 3.5.1.11) with partial spacer segment was identified. As a final proteolytic step, the deletion of this spacer segment was revealed to be a first-order reaction, suggesting an intramolecular Ntn mechanism for the auto-proteolysis. Accordingly, the different proteolytic sites in the acylase precursor indicate a substrate entering pathway along the spacer peptide. Second, bromoacyl-7ACA can interact with penicillin G acylase (EC 3.5.1.11) in two distinguish aspects, to be hydrolyzed as a substrate analogue and to affinity alkylate the conserved Trpb4 as a product analogue. The kinetic correlation between these two reactions suggests a channel opening from Serb1 to Trpb4, responsible for the main product leaving. These two reaction trajectories relaying at the active centre, together with the crystal structures (5-10), predict an engulfing dynamic involving pocket constriction and channel opening

Snyder's Model -- de Sitter Special Relativity Duality and de Sitter Gravity

Between Snyder's quantized space-time model in de Sitter space of momenta and the \dS special relativity on \dS-spacetime of radius $R$ with Beltrami coordinates, there is a one-to-one dual correspondence supported by a minimum uncertainty-like argument. Together with Planck length $\ell_P$, $R\simeq (3/\Lambda)^{1/2}$ should be a fundamental constant. They lead to a dimensionless constant $g{\sim\ell_PR^{-1}}=(G\hbar c^{-3}\Lambda/3)^{1/2}\sim 10^{-61}$. These indicate that physics at these two scales should be dual to each other and there is in-between gravity of local \dS-invariance characterized by $g$. A simple model of \dS-gravity with a gauge-like action on umbilical manifolds may show these characters. It can pass the observation tests and support the duality.Comment: 32 page

THE DYNAMIC ANALYSIS OF THE APPLIED FORCE ON JAVELIN DURING FINAL THRUST BY AN ELITE JAVELIN THROWER

According to the javelin rules, a throw is valid only if the tip strikes the ground before any other part of the javelin. So it is important to precisely control the applied force on javelin for further distance and tip-first landing. Two synchronized Redlake high-speed cameras (250 Hz) were used to videotape an elite thrower; a javelin with three fixed non-collinear markers was used in experiment. The aerodynamics and Newton-Euler equation were taken into account in the 3D inverse dynamic analysis. The results showed that the force was mainly on the axial direction as the whole hand gripped the javelin. However, as the portion of hand touching the javelin became lesser, the direction of force was changed from axial to lateral direction. The lateral torque was significantly larger than axial torque during the whole phase, and their maxima were 24.08 and 1.31 Nm, respectively. The results measured by this method were similar to those by force sensor, and it could be suitable for use in further researches