PMID- 24364418
OWN - NLM
STAT- MEDLINE
DCOM- 20140921
LR  - 20140108
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Linking)
VI  - 136
IP  - 1
DP  - 2014 Jan 8
TI  - Evidence for the existence of elaborate enzyme complexes in the Paleoarchean era.
PG  - 122-9
LID - 10.1021/ja4115677 [doi]
AB  - Due to the lack of macromolecular fossils, the enzymatic repertoire of extinct 
      species has remained largely unknown to date. In an attempt to solve this 
      problem, we have characterized a cyclase subunit (HisF) of the imidazole glycerol 
      phosphate synthase (ImGP-S), which was reconstructed from the era of the last 
      universal common ancestor of cellular organisms (LUCA). As observed for 
      contemporary HisF proteins, the crystal structure of LUCA-HisF adopts the 
      (betaalpha)8-barrel architecture, one of the most ancient folds. Moreover, LUCA-HisF (i) 
      resembles extant HisF proteins with regard to internal 2-fold symmetry, active 
      site residues, and a stabilizing salt bridge cluster, (ii) is thermostable and 
      shows a folding mechanism similar to that of contemporary (betaalpha)8-barrel enzymes, 
      (iii) displays high catalytic activity, and (iv) forms a stable and functional 
      complex with the glutaminase subunit (HisH) of an extant ImGP-S. Furthermore, we 
      show that LUCA-HisF binds to a reconstructed LUCA-HisH protein with high 
      affinity. Our findings suggest that the evolution of highly efficient enzymes and 
      enzyme complexes has already been completed in the LUCA era, which means that 
      sophisticated catalytic concepts such as substrate channeling and allosteric 
      communication existed already 3.5 billion years ago.
FAU - Reisinger, Bernd
AU  - Reisinger B
AD  - Institute of Biophysics and Physical Biochemistry, University of Regensburg , 
      Universitatsstrasse 31, D-93053 Regensburg, Germany.
FAU - Sperl, Josef
AU  - Sperl J
FAU - Holinski, Alexandra
AU  - Holinski A
FAU - Schmid, Veronika
AU  - Schmid V
FAU - Rajendran, Chitra
AU  - Rajendran C
FAU - Carstensen, Linn
AU  - Carstensen L
FAU - Schlee, Sandra
AU  - Schlee S
FAU - Blanquart, Samuel
AU  - Blanquart S
FAU - Merkl, Rainer
AU  - Merkl R
FAU - Sterner, Reinhard
AU  - Sterner R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131223
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
RN  - 0 (Multienzyme Complexes)
RN  - EC 3.5.1.- (imidazole glycerol phosphate synthase)
RN  - EC 3.5.4.- (Aminohydrolases)
SB  - IM
MH  - Aminohydrolases/chemistry/genetics/metabolism
MH  - Archaea/enzymology/genetics
MH  - Crystallography, X-Ray
MH  - *Evolution, Molecular
MH  - Extinction, Biological
MH  - Models, Molecular
MH  - Multienzyme Complexes/*chemistry/*metabolism
MH  - Protein Folding
MH  - Protein Structure, Secondary
EDAT- 2013/12/25 06:00
MHDA- 2014/09/23 06:00
CRDT- 2013/12/25 06:00
PHST- 2013/12/25 06:00 [entrez]
PHST- 2013/12/25 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
AID - 10.1021/ja4115677 [doi]
PST - ppublish
SO  - J Am Chem Soc. 2014 Jan 8;136(1):122-9. doi: 10.1021/ja4115677. Epub 2013 Dec 23.