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000890392 1001_ $$00000-0003-2248-3544$$aPerez-Garcia, Pablo$$b0
000890392 245__ $$aA promiscuous ancestral enzyme´s structure unveils protein variable regions of the highly diverse metallo-β-lactamase family
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000890392 520__ $$aThe metallo-β-lactamase fold is an ancient protein structure present in numerous enzyme families responsible for diverse biological processes. The crystal structure of the hyperthermostable crenarchaeal enzyme Igni18 from Ignicoccus hospitalis was solved at 2.3 Å and could resemble a possible first archetype of a multifunctional metallo-β-lactamase. Ancestral enzymes at the evolutionary origin are believed to be promiscuous all-rounders. Consistently, Igni18´s activity can be cofactor-dependently directed from β-lactamase to lactonase, lipase, phosphodiesterase, phosphotriesterase or phospholipase. Its core-domain is highly conserved within metallo-β-lactamases from Bacteria, Archaea and Eukarya and gives insights into evolution and function of enzymes from this superfamily. Structural alignments with diverse metallo-β-lactamase-fold-containing enzymes allowed the identification of Protein Variable Regions accounting for modulation of activity, specificity and oligomerization patterns. Docking of different substrates within the active sites revealed the basis for the crucial cofactor dependency of this enzyme superfamily.
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000890392 7001_ $$0P:(DE-HGF)0$$aKobus, Stefanie$$b1
000890392 7001_ $$0P:(DE-HGF)0$$aGertzen, Christoph G. W.$$b2
000890392 7001_ $$00000-0002-7076-5936$$aHoeppner, Astrid$$b3
000890392 7001_ $$0P:(DE-HGF)0$$aHolzscheck, Nicholas$$b4
000890392 7001_ $$0P:(DE-Juel1)169449$$aStrunk, Christoph Heinrich$$b5
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000890392 7001_ $$0P:(DE-Juel1)131457$$aJaeger, Karl-Erich$$b7
000890392 7001_ $$0P:(DE-Juel1)172663$$aGohlke, Holger$$b8
000890392 7001_ $$0P:(DE-Juel1)131480$$aKovacic, Filip$$b9
000890392 7001_ $$00000-0003-0780-9251$$aSmits, Sander H. J.$$b10
000890392 7001_ $$00000-0001-7617-7396$$aStreit, Wolfgang R.$$b11
000890392 7001_ $$00000-0002-7499-5325$$aChow, Jennifer$$b12$$eCorresponding author
000890392 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-021-01671-8$$gVol. 4, no. 1, p. 132$$n1$$p132$$tCommunications biology$$v4$$x2399-3642$$y2021
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