Poelarends G J, Veetil V Puthan, Whitman C P
Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.
Cell Mol Life Sci. 2008 Nov;65(22):3606-18. doi: 10.1007/s00018-008-8285-x.
Tautomerase superfamily members have an amino-terminal proline and a beta-alpha-beta 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.
互变异构酶超家族成员具有一个氨基末端脯氨酸和一个β-α-β折叠结构，包括4-草酰巴豆酸互变异构酶（4-OT）、5-（羧甲基）-2-羟基粘康酸异构酶（CHMI）、反式和顺式3-氯丙烯酸脱卤酶（分别为CaaD和顺式-CaaD）、丙二酸半醛脱羧酶（MSAD）以及巨噬细胞迁移抑制因子（MIF），后者具有苯丙酮酸互变异构酶（PPT）活性。Pro-1在某些成员中是一种碱（4-OT、CHMI、MIF的PPT活性）或酸（CaaD、顺式-CaaD、MSAD）。催化机制的组成部分已被确定，并提出了机制假说。新同源物的表征表明这些机制并不完整。4-OT、CaaD、顺式-CaaD和MSAD还具有混杂活性，其中CaaD、顺式-CaaD和MSAD具有水合酶活性，CaaD和顺式-CaaD具有PPT活性，4-OT具有CaaD和顺式-CaaD活性。这些共享的混杂活性为从共同祖先的趋异进化提供了证据，暗示了机制关系，并表明催化混杂在新酶的出现中起作用。
