cd07937

Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain

CDD entry
Member databaseCDD
CDD typedomain
Short nameDRE_TIM_PC_TC_5S
SetTIM

Description

This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
[3, 4, 2, 5, 1]

References

1.Expression and crystallization of several forms of the Propionibacterium shermanii transcarboxylase 5S subunit. Hall PR, Zheng R, Pusztai-Carey M, van den Akker F, Carey PR, Yee VC. Acta Crystallogr. D Biol. Crystallogr. 60, 521-3, (2004). View articlePMID: 14993680

2.Transcarboxylase: one of nature's early nanomachines. Carey PR, Sonnichsen FD, Yee VC. IUBMB Life 56, 575-83, (2004). PMID: 15814455

3.Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit. Hall PR, Zheng R, Antony L, Pusztai-Carey M, Carey PR, Yee VC. EMBO J. 23, 3621-31, (2004). View articlePMID: 15329673

4.A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A. Yu LP, Xiang S, Lasso G, Gil D, Valle M, Tong L. Structure 17, 823-32, (2009). View articlePMID: 19523900

5.Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli. Thornton CG, Kumar GK, Haase FC, Phillips NF, Woo SB, Park VM, Magner WJ, Shenoy BC, Wood HG, Samols D. J. Bacteriol. 175, 5301-8, (1993). View articlePMID: 8366018

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