Pyruvate carboxylase: Difference between revisions

Latest revision as of 10:38, 25 January 2023

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Pyruvate carboxylase complex with CoA, ATP-gamma-S, glycerol, Mg++ (green), Zn++ (grey) Cl- (green) (PDB code 2qf7)

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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 pyruvate to form oxaloacetate (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^[1] .

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^[2]. Deregulation of PC expression is associated with type 2 diabetics and tumorgenesis in several cancers^[3] .

Structural highlights

The 3D structure of PC shows its 4 domains: BC, CT, allosteric effector and BCCP.

The ATP moiety active site is in the BC domain and contains 2 Mg++ ions. Water molecules shown as red spheres. Close up view of 2 Mg++ coordination sites.

The effector CoA is bound to the BC domain and the allosteric effector domain^[4].

3D structures of pyruvate carboxylase

Pyruvate carboxylase 3D structures

↑ 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:https://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:https://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:https://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

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] 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:https://dx.doi.org/10.1042/BJ20080709

[2] 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:https://dx.doi.org/10.1002/humu.23742

[3] 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:https://dx.doi.org/10.1007/s00109-018-1622-0

[4] 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

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-<StructureSection load='2qf7' size='340' side='right' caption='Caption for this structure' scene=''>
+<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'>
-This is a default text for your page '''Pyruvate carboxylase'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
-You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
-== Function ==
+==Function==
-== Disease ==
+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> .
-== Relevance ==
+See also [[Major metabolic pathways converging on the citric acid cycle]].
-== Structural highlights ==
+==Disease==
-This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
+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> .
+==Structural highlights==
+The 3D structure of PC shows its <scene name='93/939263/Cv/3'>4 domains: BC, CT, allosteric effector and BCCP</scene>.
+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>.
+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>.
+==3D structures of pyruvate carboxylase==
+[[Pyruvate carboxylase 3D structures]]
 </StructureSection>
 == References ==
 <references/>
+[[Category:Topic Page]]

Pyruvate carboxylase: Difference between revisions

Latest revision as of 10:38, 25 January 2023

Contents

Function

Disease

Structural highlights

3D structures of pyruvate carboxylase

References

Proteopedia Page Contributors and Editors (what is this?)

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