Positively charged endogenous and exogenous organic compounds of diverse chemical structures are transported by polyspecific organic cation transporters (OCT). In two contributions to the May 2005 issue of Molecular Pharmacology, amino acid residues within the fourth and tenth transmembrane helices of rat OCT1 are described that contribute to cation and corticosterone binding. In a three-dimens...

LeuT-like fold Na-dependent secondary active transporters form a large family of integral membrane proteins that transport various substrates against their concentration gradient across lipid membranes, using the free energy stored in the downhill concentration gradient of sodium ions. These transporters play an active role in synaptic transmission, the delivery of key nutrients, and the mainte...

The aspartic protease -secretase (BACE) cleaves the amyloid precursor protein into a 42 residue -peptide, which is the principal biochemical marker of Alzheimer’s disease. Multiple explicit-water molecular dynamics simulations of the apo and inhibitor bound structures of BACE indicate that both openand closed-flap conformations are accessible at room temperature and should be taken into account...

The binding of the regulatory subunit to the catalytic subunit of protein kinase is known to completely inhibit the catalytic activity by formation of the inactive holoenzyme. Magnetic resonance methods have been used to compare the binding of ADP, Mn2+, and a peptide substrate and substrate analog to the holoenzyme or to the catalytic subunit. ADP and MnADP are found to bind to the holoenzyme ...

Milk xanthine oxidase exhibits a broad substrate specificity that includes purines, aldehydes, and pteridines (1). The mechanism of substrate oxidation, particularly that of purines, has been the subject of several studies (2-4). The present report concerns the observation of a new class of substrates, quaternary heterocyclic compounds, which are oxidized at pH values above 9.6. A partial list ...

Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/TPXK motifs, indicating highly s...

BACKGROUND Archaemetzincins are metalloproteases occurring in archaea and some mammalia. They are distinct from all the other metzincins by their extended active site consensus sequence HEXXHXXGXXHCX(4)CXMX(17)CXXC featuring four conserved cysteine residues. Very little is known about their biological importance and structure-function relationships. PRINCIPAL FINDINGS Here we present three cr...

It has been suggested that the fundamental feature that distinguishes enzymes from simple chemical catalysts is the ability of enzymes to use binding interactions for catalysis. Results with the Tetrahymena group I RNA enzyme described herein directly demonstrate the catalytic contributions of binding interactions. With wild-type ribozyme, specific functional groups at a distance from the site ...

Milk xanthine oxidase exhibits a broad substrate specificity that includes purines, aldehydes, and pteridines (1). The mechanism of substrate oxidation, particularly that of purines, has been the subject of several studies (2-4). The present report concerns the observation of a new class of substrates, quaternary heterocyclic compounds, which are oxidized at pH values above 9.6. A partial list ...

Highly purified a-thrombin has been chemically modified in an attempt to determine which features of the molecule are important for normal platelet-thrombin interactions. Modifying agents included diisopropylphosphorofluoridate and 1-chloro-3-tosylamido-7-amino-L-2-heptanone, which modify serine and histidine, respectively, at the catalytic site, as well as N-bromosuccinimide and Z-hydroxy-5-ni...