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Since monosodium urate (NaU) may play an important etiologic role in the formation of renal stones containing Ca in patients with hyperuricosuria, the current studies were undertaken to define some of the physiocochemical factors which determine the formation of NaU. In solutions containing Na, uric acid was rapidly transformed to NaU at pH greater than 6.… (More)
Matrix metalloproteinase-1 (MMP-1) is an instigator of collagenolysis, the catabolism of triple helical collagen. Previous studies have implicated its hemopexin (HPX) domain in binding and possibly destabilizing the collagen substrate in preparation for hydrolysis of the polypeptide backbone by the catalytic (CAT) domain. Here, we use biophysical methods to… (More)
Seeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro. Seeds of uric acid had a small or no effect. The results could account for the formation of calcium stones among patients with hyperuricosuria and normocalciuria.
SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells. Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase activity that reduces cellular dNTP to a level where reverse transcriptase cannot function, although alternative mechanisms have been proposed recently. Here, we present combined structural and… (More)
The development of deoxynucleoside triphosphate (dNTP)-based drugs requires a quantitative understanding of any inhibition, activation, or hydrolysis by off-target cellular enzymes. SAMHD1 is a regulatory dNTP-triphosphohydrolase that inhibits HIV-1 replication in human myeloid cells. We describe here an enzyme-coupled assay for quantifying the activation,… (More)