Malaria is a highly prevalent infectious disease caused by the Plasmodium parasite transmitted through Anopheles mosquitoes, which poses significant public health challenge worldwide, including in Indonesia. Therefore, study was conducted to identify potential drug compounds from Carica papaya plant that could inhibit various antimalarial proteins or receptors, such as falciparum DXR reductase ...

5-Formyltetrahydrofolate was found to reverse the binding of methotrexate to dihydrofolate redactase in the Ehrlich ascites tumor in vitro. When cells pretreated with methotrexate were resuspended in methotrexate-free buffer containing 5-formyltetrahydrofolate (or 5-methyltetrahydrofolate), net dissociation of the antifolate from the enzyme was observed. Methotrexate associated with the enzyme ...

When chicken liver dihydrofolate reductase reacts with an excess of sodium tetrathionate, 1 mol of thiosulfate becomes covalently attached to the single sulfhydryl group of the enzyme. The identity of the thiosulfate was established by obtaining 1:l binding independently with both innerand outer-labeled [36S]tetrathionate. The thiosulfate form of the enzyme has 5to 10-fold more activity than n...

Mitochondrial protein import depends on heterooligomeric translocases in the outer and inner membranes. Using substrates consisting of various lengths N-terminal part mitochondrial dihydrolipoamide dehydrogenase (LDH) fused to dihydrofolate reductase we present an vivo analysis showing that Trypanosoma brucei at least 96 aa mature LDH are required efficiently produce intermediate spans both tra...

INTRODUCTION 5-Fluorouracil and methotrexate are antimetabolites widely used in the treatment of neoplastic disease. They act by inactivating the two enzymes involved in the biosynthesis of the pyrimidine nucleotide 2’-deoxythymidine 5’-monophosphate, namely thymidylate synthase and dihydrofolate reductase. The three dimensional structure of each enzyme is known and the mechanisms of the reacti...

The effects of ligand binding on antibody complex formation of Lactobacillus casei dihydrofolate reductase have been investigated. Binary complexes containing either substrate and inhibitors or NADP+ and NADPH together with ternary complexes containing inhibitors and coenzyme were examined. Whereas substrate and inhibitor binding alone show no effect, the binding of coenzyme reduces antibody co...

The de novo thymidylate biosynthetic pathway in mammalian cells translocates to the nucleus for DNA replication and repair and consists of the enzymes serine hydroxymethyltransferase 1 and 2α (SHMT1 and SHMT2α), thymidylate synthase, and dihydrofolate reductase. In this study, we demonstrate that this pathway forms a multienzyme complex that is associated with the nuclear lamina. SHMT1 or SHMT2...

Many new antifolate compounds with unique clinical properties are currently in clinical development. Some of these agents have been rationally designed to circumvent known mechanisms of resistance to methotrexate, the most useful and extensively studied antifolate in clinical practice. Resistance to methotrexate can result from decreased active transport into cells, decreased polyglutamation re...

Honeybee prepromelittin (70 amino acid residues), the precursor of an eukaryotic secretory protein, and a hybrid protein between prepromelittin and mouse dihydrofolate reductase (257 amino acid residues) were expressed in Escherichia coli and characterized with respect to their requirements for transport across the plasma membrane. Both precursor proteins are posttranslationally processed and e...

How evolution has affected enzyme function is a topic of great interest in the field of biophysical chemistry. Evolutionary changes from Escherichia coli dihydrofolate reductase (ecDHFR) to human dihydrofolate reductase (hsDHFR) have resulted in increased catalytic efficiency and an altered dynamic landscape in the human enzyme. Here, we show that a subpicosecond protein motion is dynamically c...