Journal Article

FZJ-2021-00925

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A promiscuous ancestral enzyme´s structure unveils protein variable regions of the highly diverse metallo-β-lactamase family

Perez-Garcia, P. ; Kobus, S. ; Gertzen, C. G. W. ; Hoeppner, A. ; Holzscheck, N. ; Strunk, C. H. ; Huber, H. ; Jaeger, K.-E.FZJ* ; Gohlke, H.FZJ* ; Kovacic, F.FZJ* ; Smits, S. H. J. ; Streit, W. R. ; Chow, J. (Corresponding author)

2021
Springer Nature London

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/27113  doi:10.1038/s42003-021-01671-8

Abstract: The 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.

---

Contributing Institute(s):

1. John von Neumann - Institut für Computing (NIC)
2. Jülich Supercomputing Center (JSC)
3. Strukturbiochemie (IBI-7)
4. Institut für Molekulare Enzymtechnologie (HHUD) (IMET)

Research Program(s):

1. 5111 - Domain-Specific Simulation Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)
3. DFG project 417919780 - Zentrum für strukturelle Studien (417919780)

Appears in the scientific report 2021

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---