TY - JOUR
T1 - Cobalamin-Dependent and Cobalamin-Independent Methionine Synthases
T2 - Are There Two Solutions to the Same Chemical Problem?
AU - Matthews, Rowena G.
AU - Smith, April E.
AU - Zhou, Zhaohui S.
AU - Taurog, Rebecca E.
AU - Bandarian, Vahe
AU - Evans, John C.
AU - Ludwig, Martha
PY - 2003
Y1 - 2003
N2 - Two enzymes in Escherichia coli, cobalamin-independent methionine synthase (MetE) and cobalamin-dependent methionine synthase (MetH), catalyze the conversion of homocysteine (Hcy) to methionine using N(5) -methyltetrahydrofolate (CH3-H4folate) as the Me donor. Despite the absence of sequence homology, these enzymes employ very similar catalytic strategies. In each case, the pKa for the SH group of Hcy is lowered by coordination to Zn2+, which increases the concentration of the reactive thiolate at neutral pH. In each case, activation of CH3-H4folate appears to involve protonation at N(5). CH3-H4folate remains unprotonated in binary E · CH3-H4folate complexes, and protonation occurs only in the ternary E · CH3-H4folate · Hcy complex in MetE, or in the ternary E · CH3-H4folate · cob(I)alamin complex in MetH. Surprisingly, the similarities are proposed to extend to the structures of these two unrelated enzymes. The structure of a homologue of the Hcy-binding region of MetH, betaine-homocysteine methyltransferase, has been determined. A search of the three-dimensional-structure data base by means of the structure-comparison program DALI indicates similarity of the BHMT structure with that of uroporphyrin decarboxylase (UroD), a homologue of the MT2-A and MT2-M proteins from Archaea. which catalyze Me transfers from methylcorrinoids to coenzyme M and share the Zn-binding scaffold of MetE. Here, we present a model for the Zn binding site of MetE, obtained by grafting the Zn ligands of MT2-A onto the structure of UroD.
AB - Two enzymes in Escherichia coli, cobalamin-independent methionine synthase (MetE) and cobalamin-dependent methionine synthase (MetH), catalyze the conversion of homocysteine (Hcy) to methionine using N(5) -methyltetrahydrofolate (CH3-H4folate) as the Me donor. Despite the absence of sequence homology, these enzymes employ very similar catalytic strategies. In each case, the pKa for the SH group of Hcy is lowered by coordination to Zn2+, which increases the concentration of the reactive thiolate at neutral pH. In each case, activation of CH3-H4folate appears to involve protonation at N(5). CH3-H4folate remains unprotonated in binary E · CH3-H4folate complexes, and protonation occurs only in the ternary E · CH3-H4folate · Hcy complex in MetE, or in the ternary E · CH3-H4folate · cob(I)alamin complex in MetH. Surprisingly, the similarities are proposed to extend to the structures of these two unrelated enzymes. The structure of a homologue of the Hcy-binding region of MetH, betaine-homocysteine methyltransferase, has been determined. A search of the three-dimensional-structure data base by means of the structure-comparison program DALI indicates similarity of the BHMT structure with that of uroporphyrin decarboxylase (UroD), a homologue of the MT2-A and MT2-M proteins from Archaea. which catalyze Me transfers from methylcorrinoids to coenzyme M and share the Zn-binding scaffold of MetE. Here, we present a model for the Zn binding site of MetE, obtained by grafting the Zn ligands of MT2-A onto the structure of UroD.
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U2 - 10.1002/hlca.200390329
DO - 10.1002/hlca.200390329
M3 - Article
AN - SCOPUS:0347717891
VL - 86
SP - 3939
EP - 3954
JO - Helvetica Chimica Acta
JF - Helvetica Chimica Acta
SN - 0018-019X
IS - 12
ER -