Acetyl-CoA carboxylase

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<StructureSection load='1bdo' size='450' side='right' scene='49/492046/Cv/1' caption=''>
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<StructureSection load='1bdo' size='450' side='right' scene='49/492046/Cv/1' caption='E. coli Acetyl-CoA carboxylase biotinyl domain complex with biotin (PDB code [[1bdo]]) '>
== Function ==
== Function ==
'''Acetyl-CoA carboxylase''' (ACC) catalyzes the irreversible carboxylation of acetyl-CoA to malonyl-CoA. Malonyl-CoA is a building block in in the biosynthesis of fatty acids. ACC is biotin- and ATP-dependent enzyme. In mammals, 2 forms of ACC exist. ACC1 and ACC2 differ in their tissue distribution and function.
'''Acetyl-CoA carboxylase''' (ACC) catalyzes the irreversible carboxylation of acetyl-CoA to malonyl-CoA. Malonyl-CoA is a building block in in the biosynthesis of fatty acids. ACC is biotin- and ATP-dependent enzyme. In mammals, 2 forms of ACC exist. ACC1 and ACC2 differ in their tissue distribution and function.
== Structural highlights ==
== Structural highlights ==
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ACC is a multi-subunit enzyme in prokaryotes and plants. Each subunit catalyzes different reaction. These are – '''biotin carboxylase''' (BC) which carboxylates the biotin prosthetic group see [[Biotin carboxylase]], '''biotin carboxyl carrier protein''' (BCCP) which is linked covalently to biotin and '''carboxyltransferase''' (CT) which transfers the carboxyl group from biotin to acetyl-CoA. In eukaryotes these functions are performed by a single polypeptide chain. The biotindyl domain (residues 891-964 in human) transfers an activated carboxyl group from the BC domain to the CT domain. <scene name='49/492046/Cv/2'>E.coli biotin carboxylase complex with biotin</scene> ([[1bdo]]) is shown.
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ACC is a multi-subunit enzyme in prokaryotes and plants. Each subunit catalyzes different reaction. These are – '''biotin carboxylase''' (BC) which carboxylates the biotin prosthetic group see [[Biotin carboxylase]], '''biotin carboxyl carrier protein''' (BCCP) which is linked covalently to biotin and '''carboxyltransferase''' (CT) which transfers the carboxyl group from biotin to acetyl-CoA. In eukaryotes these functions are performed by a single polypeptide chain. The biotindyl domain (residues 891-964 in human, 75-156 in E.coli) transfers an activated carboxyl group from the BC domain to the CT domain. <scene name='49/492046/Cv/2'>E.coli biotin carboxylase complex with biotin</scene> ([[1bdo]]) is shown.
== Disease ==
== Disease ==
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*Biotin carboxyl carrier protein (BCCP) domain
*Biotin carboxyl carrier protein (BCCP) domain
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**[[1a6x]] EcBCCP C terminal – ''Escherichia coli'' – NMR<BR />
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**[[1bnc]], [[1dv1]] - EcBCCP – ''Escherichia coli''<br />
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**[[2dn8]] – hBCCP2 – human - NMR<BR />
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**[[2gps]], [[2gpw]], [[3g8d]] - EcBCCP (mutant)<br />
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**[[1a6x]], [[3bdo]] – EcBCCP biotinyl domain – NMR<BR />
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**[[2dn8]] – hBCCP2 residues 8-94 – human - NMR<BR />
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**[[2kcc]] - hBCCP2 residues 891-964 – NMR<br />
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**[[3glk]], [[3jrw]] – hBCCP2<br />
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**[[4hq6]] – hBCCP2 (mutant)<br />
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**[[2yl2]] – hBCCP1<br />
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**[[2c00]] – BCCP – ''Pseudomonas aeruginosa''<br />
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**[[1w93]] – yBCCP – yeast <br />
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* Biotin carboxyl carrier protein (BCCP) subunit complex
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**[[1bdo]] - EcBCCP + biotin <br />
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**[[2bdo]] - EcBCCP + biotin – NMR<br />
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**[[1w96]] – yBCCP + soraphen <br />
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**[[3gid]], [[3jrx]] – hBCCP2 + soraphen <br />
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**[[2j9g]] – EcBCCP + AMPPNP + ADP<br />
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**[[1dv2]] – EcBCCP (mutant) + ATP<br />
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**[[3rup]] - EcBCCP + Ca + ADP<br />
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**[[3rv3]] - EcBCCP + Mg + ADP<br />
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**[[3rv4]] - EcBCCP + bicarbonate + Mg-ADP<br />
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**[[3g8c]] - EcBCCP + biotin + bicarbonate + Mg + ADP<br />
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**[[2vr1]] - EcBCCP + ATP analog<br />
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**[[2vpq]] - SaBCCP + AMPPNP <br />
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**[[2vqd]] - SaBCCP + AMPCP<br />
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**[[3ouz]] - CjBCCP + ADP – Campylobacter jejuni<br />
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**[[3ouu]] - CjBCCP + b-g-ATP<br />
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**[[4hr7]] – EcBCCP + biotin carboxyl carrier protein<br />
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**[[4mv1]] – HiBCCP + Pi + ADP – Haemophilus influenzae<br />
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**[[4mv3]] – HiBCCP + bicarbonate + AMPCP <br />
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**[[4mv4]] – HiBCCP + Mg + AMPCP <br />
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**[[4mv8]] – HiBCCP + Pi + AMPCP <br />
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**[[4mv9]] – HiBCCP + bicarbonate <br />
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**[[4mv6]], [[4mv7]] – HiBCCP + phosphoacetamide <br />
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* Biotin carboxyl carrier protein (BCCP) subunit complex with inhibitors
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**[[2v58]], [[2v59]], [[2v5a]] - EcBCCP + inhibitor<br />
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**[[2w6m]], [[2w6n]], [[2w6o]], [[2w6p]], [[2w6q]], [[2w6z]], [[2w70]], [[2w71]] - EcBCCP + fragment-based inhibitor<br />
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**[[3jzf]], [[3jzi]] - EcBCCP + benzimidazole inhibitor<br />
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**[[1w96]] – yBCCP + soraphen <br />
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**[[3ff6]] – hBCCP2 + inhibitor <br />
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**[[3gid]], [[3jrx]] – hBCCP2 + soraphen <br />
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**[[3pgq]] - CjBCCP + pinoxaden
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*Carboxyltransferase (CT) domain
*Carboxyltransferase (CT) domain

Revision as of 10:49, 11 November 2015

E. coli Acetyl-CoA carboxylase biotinyl domain complex with biotin (PDB code 1bdo)

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3D structures of acetyl-CoA carboxylase

Updated on 11-November-2015


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Michal Harel, Alexander Berchansky, Joel L. Sussman

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