Crystal structure of a methyltetrahydrofolate- and corrinoid-dependent methyltransferase

Doukov, Tzanko; Seravalli, Javier; Stezowski, John J.; Ragsdale, Stephen W.

doi:10.1016/s0969-2126(00)00172-6

Cited by 76 publications

(91 citation statements)

References 86 publications

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“…The complex of MetH with CH 3 -H 4 folate confirms several features of the model proposed for the binding of CH 3 -H 4 -folate to the homologous corrinoid͞iron-sulfur protein methyltransferase from Moorella thermoacetica (AcsE, a subunit of acetylCoA synthase) (36).…”

Section: Resultssupporting

confidence: 76%

Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase

Evans

Huddler

Hilgers

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

141

146

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Section: Resultssupporting

confidence: 76%

Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase

Evans

Huddler

Hilgers

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

141

146

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“…The structure of the fol-domain of methionine synthase shows CH 3 -H 4 folate bound near the C-terminal end of the central ␤-strands (18), and a similar position has been proposed for the binding of CH 3 -H 4 folate to MeTr (10). To correctly position the corrin-ring on top of CH 3 -H 4 folate, an arrangement between the C-terminal domain of CfsA and MeTr can be anticipated that resembles the complex between the C-terminal domain and CfsB (Fig.…”

Section: Resultsmentioning

confidence: 63%

“…The physiological methyl donor for CoFeSP Mt is the N 5 atom of (6S)-methyltetrahydrofolate (CH 3 -H 4 folate). Meth-yltransfer to the cob(I)amide center of CoFeSP Mt is facilitated by the MeTr (4), a homodimeric enzyme with two identical 28-kDa subunits with (␤␣) 8 -barrel fold (10).…”

Section: [1]mentioning

confidence: 99%

Structural insights into methyltransfer reactions of a corrinoid iron–sulfur protein involved in acetyl-CoA synthesis

Svetlitchnaia¹,

Svetlitchnyi²,

Meyer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

110

146

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acety-CoA pathway ͉ Carboxydothermus hydrogenoformans ͉ methyltransferase ͉ cobalt B 12-dependent enzymes are widespread in nature and catalyze distinct reactions. They can be grouped in three major classes: the isomerases, reductive dehalogenases, and methyltransferases (MeTrs; ref. 1). The cobalamin-dependent MeTrs play important roles in the amino acid biosynthesis in many organisms, ranging from bacteria to humans, as well as in the one-carbon metabolism of bacteria and archaea. MeTrs typically catalyze the transfer of methyl groups between organic and inorganic donors and acceptors like S-adenosylmethionine, methyltetrahydrofolate, and cobalamins. A unique methyltransfer reaction is found within the acetyl-CoA (Ljungdahl-Wood) pathway of autotrophic carbon assimilation, which operates in the anaerobic acetogenic, sulfidogenic, methanogenic, and hydrogenogenic bacteria and archaea. In the final step of the pathway, acetyl-CoA is synthesized from a methyl cation, carbon monoxide (CO), and CoA, a reaction catalyzed by the Ni-and Fe-containing enzyme acetyl-CoA synthase (ACS; for a review, see ref.2). Key to this reaction (Eq. 1) is the action of the Coand Fe-containing corrinoid iron-sulfur protein (CoFeSP) that donates the methyl group from methyl-cob(III)amide to one of the two Ni ions in the active site cluster A of ACS (3). This is the only methyltransfer reaction known with metals as donors and acceptors of the methyl group: CH 3 OCoFeSP ϩ CO ϩ CoA 3 CH 3 (CO)CoA ϩ CoFeSP. [1]CoFeSP has been isolated and characterized from the acetogenic bacterium Moorella thermoacetica (4), the methanogenic archaeon Methanosarcina thermophila (5), and the hydrogenogenic bacterium Carboxydothermus hydrogenoformans (6).C. hydrogenoformans can use CO as a sole source of energy and carbon under anaerobic chemolithoautotrophic conditions. Protons serve as terminal electron acceptor (7), and the methyl branch of the acetyl-CoA pathway is used for the assimilation of carbon (6). The oxidation of CO in this bacterium is catalyzed by two monofunctional NiFe-containing CODHs (CODHI Ch and CODHII Ch ) that harbor the [Ni-4Fe-5S] active site cluster C (7). A monomeric ACS Ch , a 1:1 molar complex of ACS Ch and CODHIII Ch , and CoFeSP Ch are expressed in functional form during the growth of C. hydrogenoformans using CO as the only substrate (6). The CoFeSP Ch from C. hydrogenoformans is a heterodimeric protein composed of a large subunit (48.4 kDa, CfsA) and a small subunit (33.9 kDa, CfsB) and harbors one molecule of the cobalt-containing corrinoid cofactor and a single The CoFeSPs from acetogens and methanogens are heterodimeric proteins sharing sequence identities of 35-53% with CoFeSP Ch from C. hydrogenoformans. CoFeSP Mt from M. thermoacetica was shown to contain two cofactors, 5-methoxybenzimidazolylcobamide (a variant of B12) and a [4Fe-4S] 2ϩ/1ϩ cluster, which gave the protein its name. For the cobamide cofactor, it was shown that neither the 5-methoxybenzimidazolyl group nor a nitrogen atom from a protein side chain is coor...

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“…1), and perhaps also MtaA. The TIM barrel fold is reminiscent of the structures of other structurally characterized methyltransferases such as the methyl-H 4 F-binding domain of MetH (28), the homocysteine-binding domain of MetH (28) and of cobalamin-independent methionine synthase (36), monomethylamine methyltransferase (29), and the methyl-H 4 F:corrinoid iron-sulfur protein methyltransferase (MeTr) (37). The most related TIM barrel is that of the homocysteine-binding domain of MetH from Thermotoga maritima with an rmsd of 3.2 Å (70% of the C ␣ -trace used).…”

Section: Structure Of Mtab and The Binding Mode Of The Catalytic Zincmentioning

confidence: 99%

“…Crystal structures of several other cobamide-dependent methyltransferases have been reported (28)(29)(30). Here we present the crystal structure of a corrinoid protein in complex with one of its catalytic methyltransferases.…”

mentioning

confidence: 94%

Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex

Hagemeier

Kr̈er

Thauer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Some methanogenic and acetogenic microorganisms have the catalytic capability to cleave heterolytically the COO bond of methanol. To obtain insight into the elusive enzymatic mechanism of this challenging chemical reaction we have investigated the methanol-activating MtaBC complex from Methanosarcina barkeri composed of the zinc-containing MtaB and the 5-hydroxybenzimidazolylcobamide-carrying MtaC subunits. Here we report the 2.5-Å crystal structure of this complex organized as a (MtaBC) 2 heterotetramer. MtaB folds as a TIM barrel and contains a novel zinc-binding motif. Zinc(II) lies at the bottom of a funnel formed at the Cterminal ␤-barrel end and ligates to two cysteinyl sulfurs (Cys-220 and Cys-269) and one carboxylate oxygen (Glu-164). MtaC is structurally related to the cobalamin-binding domain of methionine synthase. Its corrinoid cofactor at the top of the Rossmann domain reaches deeply into the funnel of MtaB, defining a region between zinc(II) and the corrinoid cobalt that must be the binding site for methanol. The active site geometry supports a S N 2 reaction mechanism, in which the COO bond in methanol is activated by the strong electrophile zinc(II) and cleaved because of an attack of the supernucleophile cob(I)amide. The environment of zinc(II) is characterized by an acidic cluster that increases the charge density on the zinc(II), polarizes methanol, and disfavors deprotonation of the methanol hydroxyl group. Implications of the MtaBC structure for the second step of the reaction, in which the methyl group is transferred to coenzyme M, are discussed.conformational change ͉ methanol metabolism ͉ x-ray structure ͉ zinc M ethanol is an abundant C 1 -compound in nature. Its major source is probably the plant cell wall component pectin from which methanol is released upon hydrolytic degradation. In oxic environments methanol is rapidly metabolized to CO 2 by aerobic methylotrophic microorganisms, which thereby prevents autooxidation to the cytotoxic formaldehyde (1). Methanol also does not accumulate in anaerobic environments, where methanogenic archaea (2) and acetogenic bacteria (3) reduce the C 1 -compound to methane, carbonylate it to acetate, and/or oxidize it to CO 2 in their energy metabolism.Methanol metabolism is initiated in methanogenic archaea by its reaction with coenzyme M (HS-CoM) to form methyl-coenzyme M (CH 3 -S-CoM) (reaction 1) (4, 5). Methyl-coenzyme M is the central intermediate for reduction to methane and oxidation to CO 2 .

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Crystal structure of a methyltetrahydrofolate- and corrinoid-dependent methyltransferase

Cited by 76 publications

References 86 publications

Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase

Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase

Structural insights into methyltransfer reactions of a corrinoid iron–sulfur protein involved in acetyl-CoA synthesis

Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex

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