3BOL

Cobalamin-dependent methionine synthase (1-566) from Thermotoga maritima complexed with Zn2+

Summary for 3BOL

• Entry DOI: 10.2210/pdb3bol/pdb
• Related: 1Q7Z 3BOF 3BQ5 3BQ6
• Descriptor: 5-methyltetrahydrofolate S-homocysteine methyltransferase, ZINC ION, POTASSIUM ION, ... (6 entities in total)
• Functional Keywords: meth, transferase, tim barrel, zinc, zinc inversion, methyltransferase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 2
• Total formula weight: 127764.81

Authors

Koutmos, M.,Smith, J.L.,Ludwig, M.L. (deposition date: 2007-12-17, release date: 2008-03-11, Last modification date: 2024-04-03)

Primary citation

Koutmos, M.,Pejchal, R.,Bomer, T.M.,Matthews, R.G.,Smith, J.L.,Ludwig, M.L.
Metal active site elasticity linked to activation of homocysteine in methionine synthases.
Proc.Natl.Acad.Sci.Usa, 105:3286-3291, 2008

PubMed Abstract: Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry upon binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.

PubMed: 18296644
DOI: 10.1073/pnas.0709960105

Experimental method

X-RAY DIFFRACTION (1.85 Å)