Biochemistry

Inversion at Zinc

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Science  28 Mar 2008:
Vol. 319, Issue 5871, pp. 1737
DOI: 10.1126/science.319.5871.1737a

One of the first things taught in organic chemistry is that a carbon atom can form bonds to four other atoms. Furthermore, these bonds point toward the vertices of a tetrahedron, with the carbon atom located at its center. The consequent variety of carbon-based molecules is, of course, the basis for biochemistry and, in particular, the biological families of macromolecules—lipids, nucleic acids, carbohydrates, and proteins. Zinc can contribute either to the catalytic power or the structural integrity of proteins and usually binds in tetrahedral fashion to the sulfur or nitrogen/oxygen atoms of its four ligands, such as cysteine or histidine.

Koutmos et al. find that the zinc atoms in the cobalamin-dependent and -independent methionine synthases MetH and MetE undergo an inversion in their geometry as these enzymes mediate the transfer of a methyl group onto homocysteine (which reaction yields methionine). Like a tetrahedral carbon in a nucleophilic substitution reaction, the zinc atom releases one of its ligands (glutamate or aspara-gine, respectively) as it reaches to make contact with the sulfur in homocysteine; this motion resembles an umbrella turning inside out on a windy day. The unanticipated flexibility of an active-site metal fits nicely with recent thinking about the importance of intrinsic protein motions for enzyme catalysis. — GJC

Proc. Natl. Acad. Sci. U.S.A. 105, 3286 (2008).

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