Reactivation of 3-dehydroquinate synthase by lanthanide cations
Reactivation of 3-dehydroquinate synthase by lanthanide cations
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DOI：
10.1021/ja974220x
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发表时间：
1998-07-22
影响因子：
15
通讯作者：
Brown, KA
中科院分区：
文献类型：
--
作者：
Moore, JD;Skinner, MA;Brown, KA
Lanthanide cations, such as Eu3+, have been increasingly used as spectroscopic probes for biological systems. However, since they are known to occur at only trace amounts in organisms, no biological role has so far been attributed to them. 1 Isomorphous substitution for octahedrally coordinated calcium ions which play noncatalytic roles in protein function in metalloproteins is wellknown. 1 Substitution of lanthanide for zinc ions, however, would not be expected because of zinc’s smaller ionic radius and its tendency to form a tetrahedral coordination state. In contrast to this view, we now report the novel binding and activation of a zinc metalloenzyme, 3-dehydroquinate (DHQ) synthase, by lanthanide cations Eu3+ and Sm3+. DHQ synthase is the second enzyme in the shikimate pathway that is ultimately responsible for the synthesis of aromatic amino acids and other ring-containing compounds. 2 DHQ synthase catalyzes the NAD+-dependent conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP, 1) to DHQ (2) according to the mechanistic pathway given in Scheme 1. 3 Interest in this enzyme stems from its unusual ability to catalyze multiple reactions in its active site, namely an oxidation, a β-elimination, a reduction, a ring-opening, and an intramolecular aldol condensation. 3, 4DHQ synthase has been demonstrated to require one divalent metal cation per monomer for activity, generally believed to be Zn2+ in vivo owing to its greater bioavailability5 and increased affinity for NAD+ in the case of the Escherichia coli enzyme. 6 On the basis of a number of factors: s (1) the sensitivity of DHQ synthase to the metal chelating agent ethylenediaminetetraacetic acid (EDTA);(2) the ability of substrate DAHP to protect the metal cation from chelation;(3) the enzyme’s varying activities in the presence of different divalent metal cations; and (4) the influence of these cations on NAD+ dissociation ratessBender, Mehdi, and Knowles6 proposed that the metal cation plays a central catalytic role throughout the enzyme mechanism. As part of an effort to obtain an isomorphous complex of DHQ synthase with a metal of sufficiently high molecular weight for
