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 | |||
Revision as of 21:18, 24 March 2011
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| 3hle, resolution 2.06Å () | |||||||||
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| Ligands: | , | ||||||||
| Related: | 1hld | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
IntroductionIntroduction
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 () 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[1].
LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic alpha-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst[1].
Exploring the structureExploring the structure
LovD is a 413-amino acid protein predicted to have an α/β hydrolase fold based on primary sequence analysis[2]. LovD has of two domains. The , which consists of residues 1–92 and 204–413, is a central seven-stranded antiparallel β-sheet flanked by α-helices on either face[1]. The is smaller, consists of residues 93–203 and is primarily α-helical[1].
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 : residues 114–125, 147–173, 243–258, 321–327, and 388–391[1].
LovD has at the following positions: C40, C49, C60, C72, C89, C216, C266, C380, and C395[3].
ReferencesReferences
- ↑ 1.0 1.1 1.2 1.3 1.4 Xie X, Tang Y. Efficient synthesis of simvastatin by use of whole-cell biocatalysis. Appl Environ Microbiol. 2007 Apr;73(7):2054-60. Epub 2007 Feb 2. PMID:17277201 doi:10.1128/AEM.02820-06
- ↑ Kennedy J, Auclair K, Kendrew SG, Park C, Vederas JC, Hutchinson CR. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science. 1999 May 21;284(5418):1368-72. PMID:10334994
- ↑ Xie X, Pashkov I, Gao X, Guerrero JL, Yeates TO, Tang Y. Rational improvement of simvastatin synthase solubility in Escherichia coli leads to higher whole-cell biocatalytic activity. Biotechnol Bioeng. 2009 Jan 1;102(1):20-8. PMID:18988191 doi:10.1002/bit.22028
10334994