Functionally diverse biotin-dependent enzymes with oxaloacetate decarboxylase activity

Lietzan, A.D.; Maurice, Martin St.

doi:10.1016/j.abb.2013.10.014

Cited by 21 publications

(21 citation statements)

References 119 publications

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“…In a structure-based clustering analysis, FAHD1 clustered together with prokaryotic members of the FAH superfamily, including fumarylpyruvate hydrolases and the oxaloacetate decarboxylase Cg1458 from C. glutamicum. Oxaloacetate decarboxylases from prokaryotic organisms are well studied and are either soluble and divalent cation-dependent (like Cg1458) or membrane-bound and dependent on sodium and biotin (20). Molecular modeling based on the established x-ray structure of FAHD1 (9) revealed that indeed the catalytic centers of FAHD1 and Cg1458 are very similar and support a common catalytic mechanism.…”

Section: Discussionmentioning

confidence: 99%

Identification of FAH Domain-containing Protein 1 (FAHD1) as Oxaloacetate Decarboxylase

Pircher¹,

Grafenstein²,

Diener³

et al. 2015

Journal of Biological Chemistry

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Background: Enzymes of the FAH superfamily catalyze a multitude of diverse chemical reactions. Results: Using molecular modeling followed by biochemical investigations, FAHD1 was identified as oxaloacetate decarboxylase. Conclusion: Our findings suggest that ODx activity can be found in eukaryotic members of the FAH superfamily. Significance: Our results identify a mammalian ODx enzyme as a so far undescribed player in mitochondrial metabolism.

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Section: Discussionmentioning

confidence: 99%

Identification of FAH Domain-containing Protein 1 (FAHD1) as Oxaloacetate Decarboxylase

Pircher¹,

Grafenstein²,

Diener³

et al. 2015

Journal of Biological Chemistry

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“…Pyruvate carboxylase (PC) is a member of biotin-containing enzyme family that catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate 25 . This is a very important anaplerotic reaction for various pivotal biochemical pathways in the central metabolism.…”

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confidence: 99%

“…The α4 form is comprised of four identical subunits, each approximately 120–130 kDa 26 . The three functional domains, biotin carboxylase (BC), carboxyltransferase (CT), and biotin carboxyl carrier protein (BCCP), are located on a single polypeptide chain 25 . The BC domain is at the N-terminus of the polypeptide chain and is responsible for binding biotin to carboxylate bicarbonate.…”

mentioning

confidence: 99%

Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome

Cao

Zhou

Zhu

et al. 2016

Sci Rep

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When retinoic acid-inducible gene 1 protein (RIG-I)-like receptors sense viral dsRNA in the cytosol, RIG-I and melanoma differentiation-associated gene 5 (MDA5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (MAVS) and initiate antiviral immune responses. In this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (PC) plays an essential role in the virus-triggered activation of nuclear factor kappa B (NF-κB) signaling mediated by MAVS. PC contributes to the enhanced production of type I interferons (IFNs) and pro-inflammatory cytokines, and PC knockdown inhibits the virus-triggered innate immune response. In addition, PC shows extensive antiviral activity against RNA viruses, including influenza A virus (IAV), human enterovirus 71 (EV71), and vesicular stomatitis virus (VSV). Furthermore, PC mediates antiviral action by targeting the MAVS signalosome and induces IFNs and pro-inflammatory cytokines by promoting phosphorylation of NF-κB inhibitor-α (IκBα) and the IκB kinase (IKK) complex, as well as NF-κB nuclear translocation, which leads to activation of interferon-stimulated genes (ISGs), including double-stranded RNA-dependent protein kinase (PKR) and myxovirus resistance protein 1 (Mx1). Our findings suggest that PC is an important player in host antiviral signaling.

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“…However, the enzyme can also catalyze the decarboxylation of oxaloacetate in the absence of other substrates. In this respect, PC also serves as a paradigm for two other biotin dependent enzymes that catalyze the decarboxylation of oxaloacetate: the oxaloacetate decarboxylase complex and transcarboxylase (reviewed in [13]). Thus, studies of oxaloacetate decarboxylation in PC are generally applicable to a range of biotin-dependent enzymes.…”

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confidence: 99%

The role of biotin and oxamate in the carboxyltransferase reaction of pyruvate carboxylase

Lietzan

Lin

Maurice

2014

Archives of Biochemistry and Biophysics

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Pyruvate carboxylase (PC) is a biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in central metabolism. During catalysis, carboxybiotin is translocated to the carboxyltransferase domain where the carboxyl group is transferred to the acceptor substrate, pyruvate. Many studies on the carboxyltransferase domain of PC have demonstrated an enhanced oxaloacetate decarboxylation activity in the presence of oxamate and it has been shown that oxamate accepts a carboxyl group from carboxybiotin during oxaloacetate decarboxylation. The X-ray crystal structure of the carboxyltransferase domain from Rhizobium etli PC reveals that oxamate is positioned in the active site in an identical manner to the substrate, pyruvate, and kinetic data are consistent with the oxamate-stimulated decarboxylation of oxaloacetate proceeding through a simple ping-pong bi bi mechanism in the absence of the biotin carboxylase domain. Additionally, analysis of truncated PC enzymes indicates that the BCCP domain devoid of biotin does not contribute directly to the enzymatic reaction and conclusively demonstrates a biotin-independent oxaloacetate decarboxylation activity in PC. These findings advance the description of catalysis in PC and can be extended to the study of related biotin-dependent enzymes.

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Functionally diverse biotin-dependent enzymes with oxaloacetate decarboxylase activity

Cited by 21 publications

References 119 publications

Identification of FAH Domain-containing Protein 1 (FAHD1) as Oxaloacetate Decarboxylase

Identification of FAH Domain-containing Protein 1 (FAHD1) as Oxaloacetate Decarboxylase

Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome

The role of biotin and oxamate in the carboxyltransferase reaction of pyruvate carboxylase

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