{
  "abstract": "Cis-isoprenyl diphosphate synthases (cis-IDSs) catalyze the synthesis of polyisoprenyl diphosphates with varying chain lengths and stereochemistry, yet the molecular mechanism underlying their substrate selectivity remains elusive. Here, we investigated VoDN3985, a cis-IDS from Viburnum odoratissimum, by combining mutagenesis, conditioned molecular dynamics (MD) simulations, and quantum mechanics/molecular mechanics (QM/MM) calculations. Conditioned MD simulations revealed substrate-dependent differences in geometric preorganization, with geranyl diphosphate (GPP) showing the highest prereactive fraction and farnesyl diphosphate (FPP) sampling more idealized allylic torsional geometries than dimethylallyl diphosphate (DMAPP). Active-site substitutions at Asn64 and His79 expanded primer tolerance to enable DMAPP utilization while preserving concerted substitution pathways in QM/MM profiles. Crucially, selectivity shift from altered configuration-dependent reaction energetics rather than barrier reductions. By decoupling dynamic conformational preorganization from intrinsic reaction-path energetics, this study provides actionable mechanistic principles for rationally engineering cis-IDS substrate selectivity.",
  "abstract_shown": true,
  "affiliations": [
    "Academy of Circular Economy, National Chung Hsing University , , No. 15, Guangming Rd, Neixing Village , ,",
    "National Chiayi University , , No. 300, Xuefu Rd, Luliao Village , East District, ,",
    "National Chung Hsing University , , No. 15, Guangming Rd, Neixing Village , ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ching-Chih Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Miao-Lin Cheng"
    },
    {
      "affs": [
        2
      ],
      "name": "Tao-Ho Chang"
    },
    {
      "affs": [
        1
      ],
      "name": "Li-Ting Ma",
      "orcid": "0000-0001-6028-0831"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8kn0fsjp6n76m.bib",
  "cited_by": 0,
  "doi": "10.1021/acsomega.6c05022",
  "fulltext_url": null,
  "id": "8kn0fsjp6n76m",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c05022/5455829/Probing-Catalytic-Residues-Responsible-for-Primer",
  "language": null,
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Plant biochemistry and biosynthesis"
    ]
  ],
  "openalex": "W7223185863",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.6c05022",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/8kn0fsjp6n76m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.1021/acsomega.6c05022",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c05022/5455829/Probing-Catalytic-Residues-Responsible-for-Primer"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Plant biochemistry and biosynthesis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Probing Catalytic Residues Responsible for Primer Substrate Reactivity in a Versatile cis -Geranylgeranyl Diphosphate Synthase",
  "title_text": "Probing Catalytic Residues Responsible for Primer Substrate Reactivity in a Versatile cis -Geranylgeranyl Diphosphate Synthase",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:39Z",
  "url": "https://research.draconitic.com/paper/8kn0fsjp6n76m",
  "venue": "ACS Omega",
  "versions": []
}