The chemical versatility of the beta-alpha-beta fold: catalytic promiscuity and divergent evolution in the tautomerase superfamily.

The chemical versatility of the beta-alpha-beta fold: catalytic promiscuity and divergent evolution in the tautomerase superfamily.
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DOI:
10.1007/s00018-008-8285-x
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发表时间:
2008-11
影响因子:
8
通讯作者:
Whitman, C. P.
Whitman, C. P.
中科院分区:
生物学1区
文献类型:
--
作者:
Poelarends, G. J.;Veetil, V. Puthan;Whitman, C. P.

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Tautomerase superfamily members have an amino-terminal proline and a β–α–β fold, and include 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), trans- and cis-3-chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively), malonate semialdehyde decarboxylase (MSAD), and macrophage migration inhibitory factor (MIF), which exhibits a phenylpyruvate tautomerase (PPT) activity. Pro-1 is a base (4-OT, CHMI, the PPT activity of MIF) or an acid (CaaD, cis-CaaD, MSAD). Components of the catalytic machinery have been identified and mechanistic hypotheses formulated. Characterization of new homologues shows that these mechanisms are incomplete. 4-OT, CaaD, cis-CaaD, and MSAD also have promiscuous activities with a hydratase activity in CaaD, cis-CaaD, and MSAD, PPT activity in CaaD and cis-CaaD, and CaaD and cis-CaaD activities in 4-OT. The shared promiscuous activities provide evidence for divergent evolution from a common ancestor, give hints about mechanistic relationships, and implicate catalytic promiscuity in the emergence of new enzymes.
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