PMID- 29309143
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20180608
LR  - 20211101
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Linking)
VI  - 140
IP  - 4
DP  - 2018 Jan 31
TI  - A Noncanonical Proximal Heme Ligand Affords an Efficient Peroxidase in a Globin 
      Fold.
PG  - 1535-1543
LID - 10.1021/jacs.7b12621 [doi]
AB  - Expanding the range of genetically encoded metal coordination environments 
      accessible within tunable protein scaffolds presents excellent opportunities for 
      the creation of metalloenzymes with augmented properties and novel activities. 
      Here, we demonstrate that installation of a noncanonical N(delta)-methyl histidine 
      (NMH) as the proximal heme ligand in the oxygen binding protein myoglobin (Mb) 
      leads to substantial increases in heme redox potential and promiscuous peroxidase 
      activity. Structural characterization of this catalytically modified myoglobin 
      variant (Mb NMH) revealed significant changes in the proximal pocket, including 
      alterations to hydrogen-bonding interactions involving the prosthetic porphyrin 
      cofactor. Further optimization of Mb NMH via a combination of rational 
      modification and several rounds of laboratory evolution afforded efficient 
      peroxidase biocatalysts within a globin fold, with activities comparable to those 
      displayed by nature's peroxidases.
FAU - Pott, Moritz
AU  - Pott M
AD  - Laboratory of Organic Chemistry, ETH Zurich , Zurich 8093, Switzerland.
FAU - Hayashi, Takahiro
AU  - Hayashi T
AD  - Laboratory of Organic Chemistry, ETH Zurich , Zurich 8093, Switzerland.
FAU - Mori, Takahiro
AU  - Mori T
AD  - Laboratory of Organic Chemistry, ETH Zurich , Zurich 8093, Switzerland.
FAU - Mittl, Peer R E
AU  - Mittl PRE
AD  - Department of Biochemistry, University of Zurich , Zurich 8057, Switzerland.
FAU - Green, Anthony P
AU  - Green AP
AUID- ORCID: 0000-0003-0454-1798
AD  - School of Chemistry & Manchester Institute of Biotechnology, The University of 
      Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.
FAU - Hilvert, Donald
AU  - Hilvert D
AUID- ORCID: 0000-0002-3941-621X
AD  - Laboratory of Organic Chemistry, ETH Zurich , Zurich 8093, Switzerland.
LA  - eng
GR  - BB/M017702/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/M027023/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/M027023/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180119
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
EDAT- 2018/01/09 06:00
MHDA- 2018/01/09 06:01
CRDT- 2018/01/09 06:00
PHST- 2018/01/09 06:00 [pubmed]
PHST- 2018/01/09 06:01 [medline]
PHST- 2018/01/09 06:00 [entrez]
AID - 10.1021/jacs.7b12621 [doi]
PST - ppublish
SO  - J Am Chem Soc. 2018 Jan 31;140(4):1535-1543. doi: 10.1021/jacs.7b12621. Epub 2018 
      Jan 19.