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1w2x

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Revision as of 13:31, 13 October 2021

Crystal structure of the carboxyltransferase domain of acetyl- coenzyme A carboxylase in complex with CP-640186

Structural highlights

1w2x is a 3 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1od2, 1od4, 1uyr, 1uys, 1uyt, 1uyv
Activity:	Acetyl-CoA carboxylase, with EC number 6.4.1.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACAC_YEAST] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Acetyl-coenzyme A carboxylases (ACCs) are important targets for the development of therapeutic agents against obesity, diabetes, and other diseases. CP-640186 is a potent inhibitor of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. It is believed to target the carboxyltransferase (CT) domain of these enzymes. Here we report the crystal structure of the yeast CT domain in complex with CP-640186. The inhibitor is bound in the active site at the interface of a dimer of the CT domain. CP-640186 has tight interactions with the putative biotin binding site in the CT domain and demonstrates a distinct mode of inhibiting the CT activity as compared to the herbicides that inhibit plant ACCs. The affinity of inhibitors for the CT domain has been assessed using kinetic and fluorescence anisotropy binding studies. The structural information identifies three regions for drug binding in the active site of CT.

Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186.,Zhang H, Tweel B, Li J, Tong L Structure. 2004 Sep;12(9):1683-91. PMID:15341732^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mishina M, Roggenkamp R, Schweizer E. Yeast mutants defective in acetyl-coenzyme A carboxylase and biotin: apocarboxylase ligase. Eur J Biochem. 1980 Oct;111(1):79-87. PMID:6108218
↑ Roggenkamp R, Numa S, Schweizer E. Fatty acid-requiring mutant of Saccharomyces cerevisiae defective in acetyl-CoA carboxylase. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1814-7. PMID:6103540
↑ Schneiter R, Hitomi M, Ivessa AS, Fasch EV, Kohlwein SD, Tartakoff AM. A yeast acetyl coenzyme A carboxylase mutant links very-long-chain fatty acid synthesis to the structure and function of the nuclear membrane-pore complex. Mol Cell Biol. 1996 Dec;16(12):7161-72. PMID:8943372
↑ Schneiter R, Guerra CE, Lampl M, Tatzer V, Zellnig G, Klein HL, Kohlwein SD. A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p. Mol Cell Biol. 2000 May;20(9):2984-95. PMID:10757783
↑ Gao H, Sumanaweera N, Bailer SM, Stochaj U. Nuclear accumulation of the small GTPase Gsp1p depends on nucleoporins Nup133p, Rat2p/Nup120p, Nup85p, Nic96p, and the acetyl-CoA carboxylase Acc1p. J Biol Chem. 2003 Jul 11;278(28):25331-40. Epub 2003 May 1. PMID:12730220 doi:http://dx.doi.org/10.1074/jbc.M301607200
↑ Zhang H, Tweel B, Li J, Tong L. Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186. Structure. 2004 Sep;12(9):1683-91. PMID:15341732 doi:10.1016/j.str.2004.07.009

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w2x"

@@ Line 3: / Line 3: @@
 <StructureSection load='1w2x' size='340' side='right'caption='[[1w2x]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1w2x]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W2X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1w2x]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W2X FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RCP:(3R)-1-(9-ANTHRYLCARBONYL)-3-(MORPHOLIN-4-YLCARBONYL)-1,4-BIPIPERIDINE'>RCP</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RCP:(3R)-1-(9-ANTHRYLCARBONYL)-3-(MORPHOLIN-4-YLCARBONYL)-1,4-BIPIPERIDINE'>RCP</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1od2|1od2]], [[1od4|1od4]], [[1uyr|1uyr]], [[1uys|1uys]], [[1uyt|1uyt]], [[1uyv|1uyv]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1od2|1od2]], [[1od4|1od4]], [[1uyr|1uyr]], [[1uys|1uys]], [[1uyt|1uyt]], [[1uyv|1uyv]]</div></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetyl-CoA_carboxylase Acetyl-CoA carboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.4.1.2 6.4.1.2] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acetyl-CoA_carboxylase Acetyl-CoA carboxylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.4.1.2 6.4.1.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w2x OCA], [http://pdbe.org/1w2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w2x RCSB], [http://www.ebi.ac.uk/pdbsum/1w2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w2x ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w2x OCA], [https://pdbe.org/1w2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w2x RCSB], [https://www.ebi.ac.uk/pdbsum/1w2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w2x ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST]] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>
+[[https://www.uniprot.org/uniprot/ACAC_YEAST ACAC_YEAST]] Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole.<ref>PMID:6108218</ref> <ref>PMID:6103540</ref> <ref>PMID:8943372</ref> <ref>PMID:10757783</ref> <ref>PMID:12730220</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1w2x

From Proteopedia

Revision as of 13:31, 13 October 2021

Crystal structure of the carboxyltransferase domain of acetyl- coenzyme A carboxylase in complex with CP-640186

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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