Sandbox Reserved 333: Difference between revisions

:Mevalonate diphosphate decarboxylase (MDD) is an important enzyme required for the biosynthesis of cholesterol and other isoprenoids in mammals, bacteria, yeast and fungi <ref name = "Byres">PMID: 17583736 </ref>. MDD is a member of the GHMP (Galactokinase, Homoserine kinase, mevalonate kinase and phosphomevalonate kinase) enzyme family, and is responsible for the conversion of mevalonate diphosphate to isopentenyl pyrophosphate with the help of 1 ATP molecule<ref name = "Byres"/> <ref name = "Voynova"> PMID: 18823933 </ref>. Even though the kinases in the GHMP family differ in quaternary structure and ability to bind a wide variety of substrates, they share a characteristic alpha/beta fold and similar sequences <ref name = "Byres"/> <ref name = "ByresMartin"> PMID: 16511101 </ref>. Some GHMP kinases exist as dimers, some as tetramers and some as monomers <ref name = "Byres"/>. The amino acid residues in MDD are highly conserved across all species, indicating the specific important activity of the enzyme <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 (Fig 2) <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"/>.