The mitochondrial citrate transport protein (CTP) is critical to energy metabolism in eukaryotic cells. We demonstrate that 1,2,3-benzenetricarboxylate (BTC), the classic and defining inhibitor of the mitochondrial CTP, is a mixed inhibitor of the reconstituted Cys-less CTP, with a strong competitive component [i.e., a competitive inhibition constant (K(ic)) of 0.12 +/- 0.02 mM and an uncompeti...

The inhibition of renal ornithine decarboxylase (ODC) by aminoglycoside antibiotics was characterized in the postmitochondrial fraction of a kidney homogenate from adult pigmented guinea pigs. Enzymatic activity was defined as the rate of decarboxylation of [14C]ornithine sensitive to a specific ODC inhibitor, alpha-difluoromethylornithine (DFMO). The Km for ornithine was 61 +/- 32 microM. Ther...

Multidrug resistance membrane pumps reduce the efficacy of chemotherapies by exporting a wide panel structurally-divergent drugs. Here, to take advantage polyspecificity human Breast Cancer Resistance Protein (BCRP/ABCG2) and dimeric nature this pump, new indenoindole-based inhibitors from monomeric α,β-unsaturated ketone 4b phenolic derivative 5a were designed. A library 18 homo/hetero-dimers ...

Fully substituted quinones including some naturally occurring oxyquinones acted as inhibitors o f yeast gluta­ thione reductase (EC 1.6.4.2). They were competitive, mixed or uncompetitive inhibitors for N A D PH , possess­ ing K j in the range o f 1 2 0 0 |iM and uncompetitive in­ hibitors for glutathione. Rhein (4,5-dioxy-9,10-anthraquinone-2-carbonic acid) and 9,10-phenanthrenequinone were th...

At neutral pH, Zn2+ is a potent and specific inhibitor of rat liver fructose 1,6-bisphosphatase (EC 3.1.3.11; D-fructose-1,6-bisphosphate 1-phosphohydrolase). Inhibition by Zn2+ is uncompetitive with respect to the activating cations Mg2+ and Mn2+, and the kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 muM. At higher c...

We report the x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan. Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the clea...

Acyl peptide hydrolase (APEH) catalyzes the removal of acetyl-amino acids from the N-terminus of peptides and cytoplasmic proteins. Due to the role played in several diseases, and to the growing interest around N-terminal acetylation, studies on APEH structure, function, and inhibition are attracting an ever increasing attention. We have therefore screened a random tetrapeptide library, N-cappe...

BACKGROUND Novel indolylarylsulfones (IASs), designed through rational structure-based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT). METHODS Here, we studied the interaction of selected halo- and nitro-substituted IAS derivatives, with the RT enzyme carrying the ...

The interaction of several biogenic amines and Compound A (2-(4-acetoxyphenyl)-2-chloro- N-methyl-ethylammonium chloride), an analogue of the active substance in a HPLC fraction isolated from the shrub, Salsola tuberculatiformis Botsch., with cytochrome P450c11 was investigated. Noradrenaline, octopamine and Compound A inhibited the type I DOC induced difference spectrum of P450c11 and elicited...