Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulfolipids of photosynthetic bacteria and plants are characterized by their unique sulfoquinovose headgroup, a derivative of glucose in which the 6-hydroxyl group is replaced by a sulfonate group. These sulfolipids have been discussed as promising anti-tumor and anti-HIV therapeutics based on their inhibition of DNA polymerase and reverse transcriptase. To study sulfolipid biosynthesis, in particular the formation of UDP-sulfoquinovose, we have combined computational modeling with biochemical methods. A database search was performed employing the derived amino acid sequence from SQD1, a gene involved in sulfolipid biosynthesis of Arabidopsis thaliana. This sequence shows high similarity to other sulfolipid biosynthetic proteins of different organisms and also to sugar nucleotide modifying enzymes, including UDP-glucose epimerase and dTDP-glucose dehydratase. Additional biochemical data on the purified SQD1 protein suggest that it is involved in the formation of UDP-sulfoquinovose, the first step of sulfolipid biosynthesis. To understand which aspects of epimerase catalysis may be shared by SQD1, we built a three-dimensional model of SQD1 using the 1.8 A crystallographic structure of UDP-glucose 4-epimerase as a template. This model predicted an NAD(+) binding site, and the binding of NAD(+) was subsequently confirmed by enzymatic assay and mass spectrometry. The active-site interactions together with biochemical data provide the basis for proposing a reaction mechanism for UDP-sulfoquinovose formation.
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PMID:Prediction of the active-site structure and NAD(+) binding in SQD1, a protein essential for sulfolipid biosynthesis in Arabidopsis. 1046 38