Pyruvate carboxylase
From Proteopedia
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| - | <StructureSection load='2qf7' size='340' side='right' caption=' | + | <StructureSection load='2qf7' size='340' side='right' caption='Pyruvate carboxylase complex with CoA, ATP-gamma-S, glycerol, Mg++ (green), Zn++ (grey) Cl- (green) (PDB code [[2qf7]])' scene='93/939263/Cv/2'> |
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| - | == Function == | + | ==Function== |
| - | == | + | Pyruvate carboxylase (PC) encoded by the gene PC is an enzyme (EC 6.4.1.1) of the ligase class that catalyzes (depending on the species) the physiologically irreversible carboxylation of <scene name='39/392339/Cv1/11'>pyruvate</scene> to form <scene name='43/430893/Cv/3'>oxaloacetate</scene> (OAA). PC is a biotin-containing enzyme. PC is a tetrameric protein containing biotin carboxylase (BC), carboxyltransferase (CT), allosteric effector (acetyl-CoA) and biotin carboxyl carrier protein (BCCP) domains. PC is regulated by acetyl-CoA and Asp. The biotin moiety transfers the carboxyl group from the biotin carboxylase active site to the carboxyltransferase active site<ref>PMID:18613815</ref> . |
| - | + | See also [[Major metabolic pathways converging on the citric acid cycle]]. | |
| - | == | + | ==Disease== |
| - | + | Mutations in the PC gene cause 3 types of clinical spectra. Type A and B are neonatal forms causing early death; type C causes mild intellectual delay<ref>PMID:30870574</ref>. Deregulation of PC expression is associated with type 2 diabetics and tumorgenesis in several cancers<ref>PMID:29362846</ref> . | |
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| + | ==Structural highlights== | ||
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| + | The 3D structure of PC shows its <scene name='93/939263/Cv/3'>4 domains: BC, CT, allosteric effector and BCCP</scene>. | ||
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| + | The <scene name='93/939263/Cv/7'>ATP moiety active site is in the BC domain and contains 2 Mg++ ions</scene>. Water molecules shown as red spheres. <scene name='93/939263/Cv/8'>Close up view of 2 Mg++ coordination sites</scene>. | ||
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| + | The <scene name='93/939263/Cv/9'>effector CoA is bound to the BC domain and the allosteric effector domain</scene><ref>PMID:17717183</ref>. | ||
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| + | ==3D structures of pyruvate carboxylase== | ||
| + | [[Pyruvate carboxylase 3D structures]] | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
| + | [[Category:Topic Page]] | ||
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References
- ↑ Jitrapakdee S, St Maurice M, Rayment I, Cleland WW, Wallace JC, Attwood PV. Structure, mechanism and regulation of pyruvate carboxylase. Biochem J. 2008 Aug 1;413(3):369-87. doi: 10.1042/BJ20080709. PMID:18613815 doi:http://dx.doi.org/10.1042/BJ20080709
- ↑ Coci EG, Gapsys V, Shur N, Shin-Podskarbi Y, de Groot BL, Miller K, Vockley J, Sondheimer N, Ganetzky R, Freisinger P. Pyruvate carboxylase deficiency type A and type C: Characterization of five novel pathogenic variants in PC and analysis of the genotype-phenotype correlation. Hum Mutat. 2019 Jun;40(6):816-827. doi: 10.1002/humu.23742. Epub 2019 Apr 13. PMID:30870574 doi:http://dx.doi.org/10.1002/humu.23742
- ↑ Lao-On U, Attwood PV, Jitrapakdee S. Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection. J Mol Med (Berl). 2018 Apr;96(3-4):237-247. doi: 10.1007/s00109-018-1622-0. Epub , 2018 Jan 23. PMID:29362846 doi:http://dx.doi.org/10.1007/s00109-018-1622-0
- ↑ St Maurice M, Reinhardt L, Surinya KH, Attwood PV, Wallace JC, Cleland WW, Rayment I. Domain architecture of pyruvate carboxylase, a biotin-dependent multifunctional enzyme. Science. 2007 Aug 24;317(5841):1076-9. PMID:17717183 doi:317/5841/1076
