PMID- 27500802
OWN - NLM
STAT- MEDLINE
DCOM- 20180510
LR  - 20220405
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Linking)
VI  - 138
IP  - 35
DP  - 2016 Sep 7
TI  - A Chemically Programmed Proximal Ligand Enhances the Catalytic Properties of a 
      Heme Enzyme.
PG  - 11344-52
LID - 10.1021/jacs.6b07029 [doi]
AB  - Enzymes rely on complex interactions between precisely positioned active site 
      residues as a mechanism to compensate for the limited functionality contained 
      within the genetic code. Heme enzymes provide a striking example of this 
      complexity, whereby the electronic properties of reactive ferryl intermediates 
      are finely tuned through hydrogen bonding interactions between proximal ligands 
      and neighboring amino acids. Here, we show that introduction of a chemically 
      programmed proximal Ndelta-methyl histidine (NMH) ligand into an engineered ascorbate 
      peroxidase (APX2) overcomes the reliance on the conserved Asp-His hydrogen 
      bonding interaction, leading to a catalytically modified enzyme (APX2 NMH), which 
      is able to achieve a significantly higher number of turnovers compared with APX2 
      without compromising catalytic efficiency. Structural, spectroscopic and kinetic 
      characterization of APX2 NMH and several active site variants provides valuable 
      insights into the role of the Asp-His-Fe triad of heme peroxidases. More 
      significantly, simplification of catalytic mechanisms through the incorporation 
      of chemically optimized ligands may facilitate efforts to create and evolve new 
      active site heme environments within proteins.
FAU - Green, Anthony P
AU  - Green AP
AD  - School of Chemistry & Manchester Institute of Biotechnology, The University of 
      Manchester , 131 Princess Street, Manchester M1 7DN, U.K.
FAU - Hayashi, Takahiro
AU  - Hayashi T
AD  - Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
FAU - Mittl, Peer R E
AU  - Mittl PR
AD  - Department of Biochemistry, University of Zurich , 8057 Zurich, Switzerland.
FAU - Hilvert, Donald
AU  - Hilvert D
AD  - Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
LA  - eng
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 - 20160826
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
RN  - 0 (Ligands)
RN  - 42VZT0U6YR (Heme)
RN  - EC 1.11.1.11 (Ascorbate Peroxidases)
SB  - IM
MH  - Ascorbate Peroxidases/*chemistry/*metabolism
MH  - *Biocatalysis
MH  - Conserved Sequence
MH  - Heme/*metabolism
MH  - Hydrogen Bonding
MH  - Ligands
MH  - Models, Molecular
MH  - Oxidation-Reduction
MH  - Protein Conformation
EDAT- 2016/08/09 06:00
MHDA- 2018/05/11 06:00
CRDT- 2016/08/09 06:00
PHST- 2016/08/09 06:00 [entrez]
PHST- 2016/08/09 06:00 [pubmed]
PHST- 2018/05/11 06:00 [medline]
AID - 10.1021/jacs.6b07029 [doi]
PST - ppublish
SO  - J Am Chem Soc. 2016 Sep 7;138(35):11344-52. doi: 10.1021/jacs.6b07029. Epub 2016 
      Aug 26.