Biological significance of C-reactive protein, the ancient acute phase functionary.

C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca.

Vector-free in vivo trans-determination of adult hepatic stem cells to insulin-producing cells.

A reduction in the number of functional β-cells is the central pathological event in diabetes. Liver and ventral pancreas differentiates simultaneously in the same general domain of cells within embryonic endoderm. In addition, the precursor cell population being bi-potential may be targeted for either pancreas or liver development.

Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.

The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules.

Crystal structure of human CD38 extracellular domain.

Human CD38 is a multifunctional protein involved in diverse functions. As an enzyme, it is responsible for the synthesis of two Ca2+ messengers, cADPR and NAADP; as an antigen, it is involved in regulating cell adhesion, differentiation, and proliferation. Besides, CD38 is a marker of progression of HIV-1 infection and a negative prognostic marker of B-CLL.

ADP-ribosyl cyclase; crystal structures reveal a covalent intermediate.

ADP-ribosyl cyclase catalyzes the elimination of nicotinamide from NAD and cyclization to cADPR, a known second messenger in cellular calcium signaling pathways. We have determined to 2.0 A resolution the structure of Aplysia cyclase with ribose-5-phosphate bound covalently at C3' and with the base exchange substrate (BES), pyridylcarbinol, bound to the active site.