Sandbox Reserved 333: Difference between revisions
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==Structure== | ==Structure== | ||
:Mevalonate diphosphate decarboxylase exists as a symmetrical dimer<ref name = "Byres"/> <ref name = "Voynova"/> <ref name ="ByresMartin"/> . The C-terminal domains of each monomer are symmetrically oriented towards one another around a solvent-filled channel <ref name = "Byres"/>. The dimer is stabilized between alpha helices 6 and 10 on the monomers, and also through salt bridge interactions, tyrosine and proline stacking, and hydrophobic interactions <ref name = "Byres"/>. The interface between the monomers is very small, with only 7% of the total surface area of the monomer engaged in the interface interaction <ref name = "Voynova"/>. This small interface between monomers is a characteristic of GHMP kinases <ref name = "Voynova"/>. Each monomer consists of a single polypeptide chain with 331 amino acid residues<ref name = "RCSB"> PMID: 6667333 </ref>. Each polypeptide chain has <scene name='Sandbox_Reserved_333/Mdd/3'>13 alpha helices and 15 beta sheets </scene> <ref name ="RCSB"/>. The active site on each monomer is a deep, highly charged cleft made up seven segments of polypeptide chain, which is located away from the other monomer, and is unaffected by dimerization <ref name = "Byres"/>. An ATP binding polypeptide segment called the P loop is also located near the active site <ref name = "Byres"/>. A total of 19 amino acid residue side chains are involved with substrate binding in the active site <ref name = "Byres"/>. | :Mevalonate diphosphate decarboxylase exists as a symmetrical dimer<ref name = "Byres"/> <ref name = "Voynova"/> <ref name ="ByresMartin"/> . The C-terminal domains of each monomer are symmetrically oriented towards one another around a solvent-filled channel <ref name = "Byres"/>. The dimer is stabilized between alpha helices 6 and 10 on the monomers, and also through salt bridge interactions, tyrosine and proline stacking, and hydrophobic interactions <ref name = "Byres"/>. The interface between the monomers is very small, with only 7% of the total surface area of the monomer engaged in the interface interaction <ref name = "Voynova"/>. This small interface between monomers is a characteristic of GHMP kinases <ref name = "Voynova"/>. Each monomer consists of a single polypeptide chain with 331 amino acid residues<ref name = "RCSB"> PMID: 6667333 </ref>. Each polypeptide chain has <scene name='Sandbox_Reserved_333/Mdd/3'>13 alpha helices and 15 beta sheets </scene> <ref name ="RCSB"/>. The active site on each monomer is a deep, highly charged cleft made up seven segments of polypeptide chain, which is located away from the other monomer, and is unaffected by dimerization <ref name = "Byres"/>. One important animo acid in the active site is Tyrosine 19 <ref name = "Byres"/>. It is strategically placed to interact with the terminal phosphate group of mevalonate diphosphate when it is bound in the active site <ref name = "Byres"/>. An ATP binding polypeptide segment called the P loop is also located near the active site <ref name = "Byres"/>. A total of 19 amino acid residue side chains are involved with substrate binding in the active site <ref name = "Byres"/>. | ||
==Reaction== | ==Reaction== | ||
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:Mevalonate diphosphate decarboxylase is a necessary enzyme in the cholesterol and isoprenoid biosynthesis pathway <ref name = "Byres"/> <ref name ="Krepkiy"> PMID: 15169949 </ref> <ref name = "Voynova"/> <ref name = "ByresMartin"/>. Without this enzyme, the cholesterol synthesis production decreases <ref name = "Krepkiy"/>, which can be detrimental to many organisms that rely on the formation of IPP for cholesterol, electron transport, membrane structures and anchors, and signaling pathways <ref name = "ByresMartin"/>. One such organism that requires MDD is the Trypanosoma bruceii, a parasite that causes [http://en.wikipedia.org/wiki/African_trypanosomiasis African Sleeping sickness] and is transmitted to the human bloodstream through the bite of the tsetse fly <ref name = "ByresMartin"/>. MDD was thought to be a potential target enzyme for an inhibitor that would disable the catalytic activity of MDD, thereby stopping IPP production and effectively killing the parasite <ref name = "ByresMartin"/>. It is believed now that the MDD found in Trypanosoma bruceii resembles human MDD too closely, and so it would be difficult to make a species specific inhibitor for MDD <ref name = "Byres"/>. | :Mevalonate diphosphate decarboxylase is a necessary enzyme in the cholesterol and isoprenoid biosynthesis pathway <ref name = "Byres"/> <ref name ="Krepkiy"> PMID: 15169949 </ref> <ref name = "Voynova"/> <ref name = "ByresMartin"/>. Without this enzyme, the cholesterol synthesis production decreases <ref name = "Krepkiy"/>, which can be detrimental to many organisms that rely on the formation of IPP for cholesterol, electron transport, membrane structures and anchors, and signaling pathways <ref name = "ByresMartin"/>. One such organism that requires MDD is the Trypanosoma bruceii, a parasite that causes [http://en.wikipedia.org/wiki/African_trypanosomiasis African Sleeping sickness] and is transmitted to the human bloodstream through the bite of the tsetse fly <ref name = "ByresMartin"/>. MDD was thought to be a potential target enzyme for an inhibitor that would disable the catalytic activity of MDD, thereby stopping IPP production and effectively killing the parasite <ref name = "ByresMartin"/>. It is believed now that the MDD found in Trypanosoma bruceii resembles human MDD too closely, and so it would be difficult to make a species specific inhibitor for MDD <ref name = "Byres"/>. | ||
==References== | ==References== | ||
<references/> | <references/> | ||
