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Biomedical subjects

B Furie

Publications and source records attributed to B Furie.

169 records · Page 10Linked to original sources
PubMed1974

The active site of staphylococcal nuclease: paramagnetic relaxation of bound nucleotide inhibitor nuclei by lanthanide ions.

The structure of 3',5'-thymidine diphosphate bound in the active site of staphylococcal nuclease (EC 3.1.4.7) was studied by measuring the relaxation rate enhancement of substrate analog nuclei by a paramagnetic metal ion. The lanthanide ion, Gd(III), was substituted for Ca(II) in the formation of the ternary complex of nuclease-Gd(III)-3',5'-thymidine diphosphate. Measurements were made of the transverse relaxation rates of protons and the longitudinal and transverse relaxation rates of the phosphorus nuclei of the bound nucleotide. Internuclear distances between the metal ion and atoms of the 3',5'-thymidine diphosphate nucleotide were determined from these data by the Solomon-Bloembergen equation. In general, these distances corresponded closely to those determined by previous x-ray crystallography of the thymidine diphosphate complex.These internuclear distances were also used with a computer program and graphics display to solve for metal-nucleotide geometries, which were consistent with the experimental data. A geometry similar to the structure of the metal-nucleotide complex bound to nuclease determined by x-ray analysis was one of the solutions to this computer modeling process. For staphylococcal nuclease, the nuclear magnetic resonance and x-ray methods yield compatible high resolution information about the structure of the active site. However, differences of uncertain significance exist between the two structures.

Binding Sites↗
PubMedDate not supplied

Detection of distinct isoform patterns of the beta-amyloid precursor protein in human platelets and lymphocytes.

Cerebral deposition of the amyloid beta-protein (A beta P), approximately 40 residue fragment of the integral membrane protein, beta-amyloid precursor protein (beta APP), has been implicated as the probable cause of some cases of familial Alzheimer's disease (AD). The parallels between A beta P deposition in AD and the deposition of certain plasma proteins in systemic amyloid diseases has heightened interest in the analysis of beta APP in circulating cells and plasma. Here, we describe distinct isoform patterns of beta APP in peripheral platelets and lymphocytes. PCR-mediated amplification of mRNA from purified platelets demonstrated the expression of all three major beta APP transcripts (beta APP770,751,695). The full-length, approximately 140 kDa form of beta APP751,770 was detected in membranes of resting and activated platelets but very little immature, approximately 122 kDa beta APP751,770 was found, suggesting a different processing of beta APP in platelets than that described in a variety of cultured cells and tissues. Platelets stimulated with thrombin, calcium ionophore, or collagen released the soluble, carboxyl-truncated form of beta APP (protease nexin-II), but no evidence for the shedding of full-length beta APP associated with platelet microparticles was found, in contrast to previous reports. As a positive control marker for microparticles, the fibrinogen receptor subunit, GPIIIa, was readily detected in platelet releasates. Resting and activated platelets contained similar amounts of the approximately 10 kDa carboxyl terminal beta APP fragment that is retained in platelet membranes following the constitutive cleavage of protease nexin-II. Nonstimulated peripheral B and T lymphocytes contained small amounts of membrane-associated mature and immature beta APP751,770. The potentially amyloidogenic full-length beta APP molecules present in circulating platelets and lymphocytes but not in microparticles could serve as a source of the microvascular A beta P deposited during aging and particularly in AD.

Adult↗