Fatty acid synthase

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== Function ==
== Function ==
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'''Fatty acid synthase''' (FAS) catalizes the synthesis of palmitate from acetyl CoA and malonyl CoA into long chain fatty acid<ref>PMID:12689621</ref> . FAS is a multi-domain enzyme. It contains an acyl carrier protein domain (ACP).
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'''Fatty acid synthase''' (FAS) catalizes the synthesis of palmitate from acetyl CoA and malonyl CoA into long chain fatty acid<ref>PMID:12689621</ref> . FAS is a multi-domain enzyme. It contains an acyl carrier protein domain (ACP). See also [[Lipid metabolism]].
== Relevance ==
== Relevance ==
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FAS is as target of anti-cancer drugs.
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FAS is as target of anti-cancer drugs. FAS from Mycobacterium tuberculosis inhibitors are possible anti-tuberculosis drugs<ref>PMID:30250274</ref> .
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== Structural insights ==
== Structural insights ==
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<scene name='48/484817/Cv/3'>Active site predominantly consists of hydrophobic/non-polar residues</scene> ({{Template:ColorKey_Hydrophobic}}, {{Template:ColorKey_Polar}}). The <scene name='48/484817/Cv/5'>long fatty acid ligand is nestled in a long groove and tunnel</scene><ref>PMID:21908709</ref>.
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<scene name='48/484817/Cv/6'>Active site predominantly consists of hydrophobic/non-polar residues</scene> ({{Template:ColorKey_Hydrophobic}}, {{Template:ColorKey_Polar}}). The <scene name='48/484817/Cv/7'>long fatty acid ligand is nestled in a long groove and tunnel</scene><ref>PMID:21908709</ref>.
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</StructureSection>
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== 3D structures of fatty acid synthase==
== 3D structures of fatty acid synthase==
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[[Fatty acid synthase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Fatty acid synthase
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**[[1kp9]] – MtFAS CmaA1 – ''Mycobacterium tuberculosis''<br />
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**[[4v8w]] – MtFAS I – Cryo-EM<br />
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**[[4v8l]] – FAS – ''Mycobacterium smegmatis'' – Cryo-EM<br />
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**[[1xkt]], [[4z49]] – hFAS thioesterase domain – human<br />
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**[[2jfd]] – hFAS MAT domain<br />
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**[[3hhd]] - hFAS KS-MAT domain<br />
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**[[4w82]] – hFAS enoyl- ACP-reductase domain<br />
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**[[2cf2]], [[2vz8]] – pFAS – pig<br />
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**[[2uv8]], [[3hmj]] – yFAS α+β subunits - yeast<br />
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**[[2pff]], [[2was]], [[2ml8]] – yFAS α subunit<br />
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**[[4v58]] – TlFAS – ''Thermomyces lanuginosus''<br />
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**[[2png]] – FAS ACP domain – rat<br />
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**[[1t8k]] – EcFAS ACP domain - ''Escherichia coli''<br />
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**[[2k92]], [[2k93]], [[2k94]] - EcFAS ACP domain – NMR<br />
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**[[5my2]] – FAS DI domain – mouse<br />
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*FAS complex with fatty acid
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**[[1kpg]] – MtFAS CmaA1 + cetyl-trimethyl-ammonium + adenosyl homocysteine<br />
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**[[1kph]] – MtFAS CmaA1 + didecyl-dimethyl-ammonium + adenosyl homocysteine<br />
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**[[1kpi]] – MtFAS CmaA2 + didecyl-dimethyl-ammonium + adenosyl homocysteine<br />
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**[[3hem]] - MtFAS CmaA1 + dioctylamine<br />
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**[[3tjm]] – hFAS thioesterase domain + fatty acid<br />
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**[[2fae]] – EcFAS ACP domain + decanethioate<br />
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**[[2fad]] – EcFAS ACP domain + heptanthioate
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*FAS complex with reactants
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**[[2jfk]] – hFAS + malonyl CoA<br />
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**[[5my0]] - mFAS + malonyl CoA<br />
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**[[4v59]] – TlFAS + NADP<BR />
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**[[2wat]] – yFAS α subunit + CoA<br />
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**[[2vz9]] – pFAS + NADP<BR />
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*FAS complex with protein
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**[[2fhs]] – EcFAS ACP domain + enoyl-ACP reductase <br />
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**[[3ejb]] - EcFAS ACP domain + biotin biosynthesis cytochrome P450-like enzyme<br />
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**[[3ejb]], [[3eje]] - EcFAS ACP domain + biotin biosynthesis cytochrome P450-like enzyme + fatty acid<br />
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**[[2cg5]] - hFAS ACP domain + AASD-PPT
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*FAS complex with inhibitor
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**[[2vkz]] - yFAS α+β subunits + cerulenin<br />
 
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**[[2px6]] – hFAS thioesterase domain + orlistat<br />
 
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**[[4piv]], [[5c37]] – hFAS (mutant) + NADP + inhibitor<br />
 
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}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human FAS thioesterase domain complex with fatty acid (PDB code 3tjm)

Drag the structure with the mouse to rotate

References

  1. ↑ Smith S, Witkowski A, Joshi AK. Structural and functional organization of the animal fatty acid synthase. Prog Lipid Res. 2003 Jul;42(4):289-317. PMID:12689621
  2. ↑ Elad N, Baron S, Peleg Y, Albeck S, Grunwald J, Raviv G, Shakked Z, Zimhony O, Diskin R. Structure of Type-I Mycobacterium tuberculosis fatty acid synthase at 3.3 A resolution. Nat Commun. 2018 Sep 24;9(1):3886. doi: 10.1038/s41467-018-06440-6. PMID:30250274 doi:http://dx.doi.org/10.1038/s41467-018-06440-6
  3. ↑ Zhang W, Chakravarty B, Zheng F, Gu Z, Wu H, Mao J, Wakil SJ, Quiocho FA. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-{gamma}-linolenic acid. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15757-62. Epub 2011 Sep 9. PMID:21908709 doi:10.1073/pnas.1112334108

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Michal Harel, Alexander Berchansky

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