The three-dimensional structure of ricin at 2.8 A

The x-ray crystallographic structure of the heterodimeric plant toxin ricin has been determined at 2.8-A resolution. The A chain enzyme is a globular protein with extensive secondary structure and a reasonably prominent cleft assumed to be the active site. The B chain lectin folds into two topologically similar domains, each binding lactose in a shallow cleft. In each site a glutamine residue forms a hydrogen bond to the OH-4 of galactose, accounting for the epimerimic specificity of binding. The interface between the A and B chains shows some hydrophobic contacts in which proline and phenylalanine side chains play a prominent role.     

Crystallization and preliminary X-ray analysis of phenylalanine hydroxylase from rat liver

Phenylalanine hydroxylase from rat liver has been crystallized from polyethylene glycol 4500 with sodium formate. The crystals are tetragonal rods and belong to space group P4(1)22 or P4(3)22 with unit cell dimensions a = b = 57.6 A and c = 304.1 A. They diffract to at least 2.4 A resolution and have one molecule per asymmetric unit.     

A Mathematical Model of a Fishery with Variable Market Price: Sustainable Fishery/Over-exploitation

We present a mathematical bioeconomic model of a fishery with a variable price. The model describes the time evolution of the resource, the fishing effort and the price which is assumed to vary with respect to supply and demand. The supply is the instantaneous catch while the demand function is assumed to be a monotone decreasing function of price. We show that a generic market price equation (MPE) can be derived and has to be solved to calculate non trivial equilibria of the model. This MPE can have 1, 2 or 3 equilibria. We perform the analysis of local and global stability of equilibria. The MPE is extended to two cases: an age-structured fish population and a fishery with storage of the resource.     

Balanol analogues probe specificity determinants and the conformational malleability of the cyclic 3',5'-adenosine monophosphate-dependent protein kinase catalytic subunit

The protein kinase family is a prime target for therapeutic agents, since unregulated protein kinase activities are linked to myriad diseases. Balanol, a fungal metabolite consisting of four rings, potently inhibits Ser/Thr protein kinases and can be modified to yield potent inhibitors that are selective-characteristics of a desirable pharmaceutical compound. Here, we characterize three balanol analogues that inhibit cyclic 3',5'-adenosine monophosphate-dependent protein kinase (PKA) more specifically and potently than calcium- and phospholipid-dependent protein kinase (PKC). Correlation of thermostability and inhibition potency suggests that better inhibitors confer enhanced protection against thermal denaturation. Crystal structures of the PKA catalytic (C) subunit complexed to each analogue show the Gly-rich loop stabilized in an "intermediate" conformation, disengaged from important phosphoryl transfer residues. An analogue that perturbs the PKA C-terminal tail has slightly weaker inhibition potency. The malleability of the PKA C subunit is illustrated by active site residues that adopt alternate rotamers depending on the ligand bound. On the basis of sequence homology to PKA, a preliminary model of the PKC active site is described. The balanol analogues serve to test the model and to highlight differences in the active site local environment of PKA and PKC. The PKA C subunit appears to tolerate balanol analogues with D-ring modifications; PKC does not. We attribute this difference in preference to the variable B helix and C-terminal tail. By understanding the details of ligand binding, more specific and potent inhibitors may be designed that differentiate among closely related AGC protein kinase family members.     

Spatial synchrony in host-parasitoid models using aggregation of variables

We consider a host-parasitoid system with individuals moving on a square grid of patches. We study the effects of increasing movement frequency of hosts and parasitoids on the spatial dynamics of the system. We show that there exists a threshold value of movement frequency above which spatial synchrony occurs and the dynamics of the system can be described by an aggregated model governing the total population densities on the grid. Numerical simulations show that this threshold value is usually small. This allows using the aggregated model to make valid predictions about global host-parasitoid spatial dynamics.