Evidence map›Paper›PMID 40787229›Full record

ArticleNature catalysis2023

Mechanistic and structural characterization of an iridium-containing cytochrome reveals kinetically relevant cofactor dynamics.

Brandon J Bloomer, Sean N Natoli, Marc Garcia-Borràs, Jose H Pereira, Derek B Hu, Paul D Adams, K N Houk, Douglas S Clark, John F Hartwig

Abstract read
In one paragraph

Article in Nature catalysis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Designing Enzymatic Reactivity with an Expanded Palette.Chembiochem : a European journal of chemical biology · 2025
    Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Brandon J BloomerDepartment of Chemistry, University of California, Berkeley, CA, USA.
Sean N NatoliDepartment of Chemistry, University of California, Berkeley, CA, USA.
Marc Garcia-BorràsDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.ORCID 0000-0001-9458-1114
Jose H PereiraJoint BioEnergy Institute, Emeryville, CA, USA.
Derek B HuDepartment of Chemistry, University of California, Berkeley, CA, USA.
Paul D AdamsJoint BioEnergy Institute, Emeryville, CA, USA.ORCID 0000-0001-9333-8219
K N HoukDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Douglas S ClarkMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.ORCID 0000-0003-1516-035X
John F HartwigDepartment of Chemistry, University of California, Berkeley, CA, USA.ORCID 0000-0002-4157-468X

Funding

Steroselectivity of Synthetically Valuable Enzyme CatalystsR01GM124480 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOUK, KENDALL N · 2018 to 2021
$1.1M
Expanding Catalytic Amination by Artificial Metalloenzymes through Cofactor Design and Directed EvolutionF32GM126652 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI NATOLI, SEAN NICHOLAS · 2017 to 2019
$118k
NIGMS NIH HHS F32 GM126652NIGMS NIH HHS R01 GM124480
6 · The paper itself

Abstract

Artificial metalloenzymes (ArMs), which contain non-native, typically synthetic, metal cofactors, are a flourishing class of biocatalyst for unnatural reactions. Although the number of these reactions is rapidly increasing, multi-faceted mechanistic studies of ArMs comprising structural, kinetic, computational and cofactor binding data to reveal detailed mechanistic information on the effects of the protein scaffold on the structure and reactivity of ArMs are more limited. Here we report the structure of an unnatural P450 analogue using X-ray diffraction. We also report the kinetic analysis of its reaction, catalyst activation during an induction period, and the origins of the stereoselectivity for the cyclopropanation of a terpene catalysed by the iridium-containing P450 variant (Ir(Me)-CYP119). Our data reveal a mechanism initiated by the flip of the cofactor from an inactive to an active conformation. This change in conformation is followed by thousands of turnovers occurring by rate-determining formation of an iridium-carbene intermediate, thereby highlighting the influence of cofactor dynamics within a single active site on an ArM-catalysed reaction.

Identifiers

PMID40787229
PMCPMC12333895

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.