Simvastatin Synthase: Difference between revisions
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{{STRUCTURE_3hle | PDB=3hle | SCENE= }} | {{STRUCTURE_3hle | PDB=3hle | SCENE= }} | ||
==Introduction== | ==Introduction== | ||
''' | '''Simvastatin synthase''' (LovD) is an enzyme isolated from the natural product biosynthetic pathways of ''Aspergillus terreus''. Simvastatin Synthase is an acyltransferase that converts the inactive monacolin J acid (<scene name='Sandbox_Reserved_316/Blah/1'>MJA</scene>) by dimethylbutyryl chloride to yield the protected form of simvastatin, which is subsequently undergoes lactonization to yield simvastatin. LovD can also | ||
synthesize the blockbuster drug simvastatin using MJA and a synthetic α-dimethylbutyryl thioester<ref name="paper1">PMID:17277201</ref>. | |||
LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic alpha-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst<ref name=" | LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic alpha-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst<ref name="paper1">PMID:17277201</ref>. | ||
==Exploring the structure== | ==Exploring the structure== | ||
LovD is a 413-amino acid protein predicted to have an α/β hydrolase fold based on primary sequence analysis<ref name="paper2">PMID:10334994</ref>. | |||
LovD has of two domains. The <scene name='Sandbox_Reserved_316/First_domain_1/1'>first domain</scene>, which consists of residues 1–92 and 204–413, is a central seven-stranded antiparallel β-sheet flanked by α-helices on either face<ref name="paper1">PMID:17277201</ref>. The <scene name='Sandbox_Reserved_316/Second_domain_1/1'>second domain</scene> is smaller, consists of residues 93–203 and is primarily α-helical<ref name="paper1">PMID:17277201</ref>. | |||
At the core of the enzyme, there are notable loops peripheral to the active site, both in size and architecture. In LovD, these loops give the impression of a ringshaped ridge or baseball catcher’s mitt over the active site with fingers composed of <scene name='Sandbox_Reserved_316/5_loops/1'>five loops</scene>: residues 114–125, 147–173, 243–258, 321–327, and 388–391<ref name="paper1">PMID:17277201</ref>. | |||
LovD has <scene name='Sandbox_Reserved_316/Cysteines/1'>nine cysteines</scene> at the following positions: C40, C49, C60, C72, C89, C216, C266, C380, and C395<ref name="paper3">PMID:18988191</ref>. | |||
==References== | ==References== | ||
<references/> | <references/> | ||
10334994 | |||