{
  "abstract": "The relationship between conformational heterogeneity and catalytic activity in enzymes is complex and poses important fundamental biological questions. Few experimental tools are available to rationally control conformations within a folded protein ensemble. Modification of the protein backbone through chemical synthesis has previously been used to alter enzyme conformational dynamics at a site essential for catalysis. Here, we explore the application of the approach to manipulate inherent conformational preferences in a dynamic helical region of an enzyme remote from its active site. Focusing on a conformationally heterogeneous helix in the de novo metal-dependent hydrolase MID1-zinc identified in prior work, a series of variants is generated with backbone-modified residues that site-specifically enhance or decrease local helical propensity. Impacts of these backbone modifications on structure, thermal stability, and esterase activity were assessed using biophysical methods. Results of these experiments reveal a complex interplay between thermal folded stability and catalytic activity in MID1-zinc. More broadly, the findings reported here validate a potentially general approach to produce enzymes with comparable oligomeric assemblies and secondary structure content but highly variable thermal stabilities and catalytic efficiencies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of Pittsburgh Pittsburgh PA 15211 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jacob A. Wolfe",
      "orcid": "0000-0001-9335-6070"
    },
    {
      "affs": [
        0
      ],
      "name": "W. Seth Horne",
      "orcid": "0000-0003-2927-1739"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3m2pacab91qsc.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra05101d",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663032/?tool=EBI",
  "id": "3m2pacab91qsc",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13663032",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7221824431",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663032/pdf/?tool=EBI",
  "pmcid": "PMC13663032",
  "pmid": "42877704",
  "published": "2026-10-14",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/3m2pacab91qsc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:20Z",
      "native_id": "PMC:PMC13663032",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13663032"
    },
    {
      "first_seen": "2026-11-01T12:23:38Z",
      "native_id": "PMC13663032",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra05101d"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Modulating thermal folded stability and catalytic activity of a de novo metalloenzyme through chemical backbone modification",
  "title_text": "Modulating thermal folded stability and catalytic activity of a de novo metalloenzyme through chemical backbone modification",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:20:52Z",
  "url": "https://research.draconitic.com/paper/3m2pacab91qsc",
  "venue": "RSC advances",
  "versions": []
}