The Ca-sensing receptor (CaSR) regulates Ca homeostasis in the body by monitoring extracellular levels of Ca ([Ca]o) and amino acids. Mutations at the hinge region of the N-terminal Venus flytrap domain (VFTD) produce either receptor inactivation (L173P, P221Q) or activation (L173F, P221L) related to hypercalcemic or hypocalcemic disorders. In this paper, we report that both L173P and P221Q mar...

Crystals of glucose-inhibited phosphorylase a shatter when exposed to substrates because the latter stabilize an active conformer. Cross-linked crystals can reanneal slowly without an alteration in the space group and can then be compared with the native crystals by x-ray diffraction. The subunits in the protein dimer move apart by about 2 A. Several long segments of polypeptide chain in the NH...

The type II fatty acid synthase pathway of Plasmodium falciparum is a validated unique target for developing novel antimalarials because of its intrinsic differences from the type I pathway operating in humans. beta-Ketoacyl-acyl carrier protein reductase is the only enzyme of this pathway that has no isoforms and thus selective inhibitors can be developed for this player of the pathway. We rep...

Some substrates of cytochrome P450 (CYP) 3A4, the most abundant CYP in the human liver responsible for the metabolism of many structurally diverse therapeutic agents, do not obey classical Michaelis-Menten kinetics and demonstrate homotropic and/or heterotropic cooperativity. The unusual kinetics and differential effects observed between substrates of this enzyme confound the prediction of drug...

Evidence has been presented that chick embryo deoxycytidylate deaminase (EC 3.5.4.12) is capable of undergoing structural changes under a variety of conditions. Rate studies revealed that inhibition of the enzyme by ethylenediaminetetraacetate markedly diminishes at 10” and below. Although EDTA does not inhibit the deaminase at lo”, the inhibition by urea, N-ethyhnaleimide, and 5,5’dithiobis(Z-...