{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3hle | PDB=3hle | SCENE= }}
==Introduction==
[[Image:svs.jpg]]'''Simvastatin synthase''' (LovD) is a 46 kDa acyltransferase found in the lovastatin biosynthetic pathway and catalyzes the final step of lovastatin biosynthesis<ref name="paper4">PMID:
17113998</ref>. Pictured here is the D5 mutant complexed with monacolin J acid (Figure 1).

This enzyme is isolated from the natural product biosynthetic pathways of ''Aspergillus terreus''. Simvastatin Synthase converts the inactive monacolin J acid (<scene name='Sandbox_Reserved_316/Blah/2'>MJA</scene>) by dimethylbutyryl chloride to yield the protected form of simvastatin (Figure 2), which subsequently undergoes lactonization to yield simvastatin<ref name="paper5">PMID:19875080</ref>.
[[Image:Sim_mja.jpg]]

LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic α-dimethylbutyryl thioester<ref name="paper1">PMID:17277201</ref>.
==Exploring the structure==
<scene name='Sandbox_Reserved_316/Svs_1/1'>TextToBeDisplayed</scene> 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>.

==Significance==
As simvastatin is an active pharmaceutical ingredient in the cholesterol-lowering drug Zocor®, its efficient synthesis from lovastatin, via LovD is intensely pursued <ref name="paper4">PMID:19875080</ref>.

==References==
<references/>

2011-04-01T22:33:53Z

Eric Ginter:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3hle | PDB=3hle | SCENE= }}
==Introduction==
'''Simvastatin synthase''' (LovD) is a 46 kDa acyltransferase found in the lovastatin biosynthetic pathway and catalyzes the final step of lovastatin biosynthesis<ref name="paper4">PMID:
17113998</ref>. Pictured here is the D5 mutant complexed with monacolin J acid (Figure 1).

This enzyme is isolated from the natural product biosynthetic pathways of ''Aspergillus terreus''. Simvastatin Synthase converts the inactive monacolin J acid (<scene name='Sandbox_Reserved_316/Blah/2'>MJA</scene>) by dimethylbutyryl chloride to yield the protected form of simvastatin (Figure 2), which 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>.

==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>.

==Exploring the structure==
As simvastatin is an active pharmaceutical ingredient in the cholesterol-lower drug Zocor®, so that efficient synthesis of simvastatin from lovastatin is highly pursued <ref name="paper1">PMID:17277201</ref>.

==References==
<references/>

Sandbox Reserved 316

2011-03-24T18:40:45Z

Eric Ginter: