1 Ocak 2023 Dergi makalesi Açık Erişim

Altiner, Pinar; Cinaroglu, Suleyman Selim; Timucin, Ahmet Can; Timucin, Emel

JSON

{
  "conceptrecid": "271297", 
  "created": "2024-06-07T16:32:39.098842+00:00", 
  "doi": "10.1038/s41598-023-45272-3", 
  "files": [
    {
      "bucket": "bb2fa4c4-2980-4f85-ad38-3f16da806e41", 
      "checksum": "md5:b38de32c111fc36af13c673a0ae21c31", 
      "key": "bib-da3092d3-2008-4f29-9e92-7aad1fb8a668.txt", 
      "links": {
        "self": "https://aperta.ulakbim.gov.tr/api/files/bb2fa4c4-2980-4f85-ad38-3f16da806e41/bib-da3092d3-2008-4f29-9e92-7aad1fb8a668.txt"
      }, 
      "size": 199, 
      "type": "txt"
    }
  ], 
  "id": 271298, 
  "links": {
    "badge": "https://aperta.ulakbim.gov.tr/badge/doi/10.1038/s41598-023-45272-3.svg", 
    "bucket": "https://aperta.ulakbim.gov.tr/api/files/bb2fa4c4-2980-4f85-ad38-3f16da806e41", 
    "doi": "https://doi.org/10.1038/s41598-023-45272-3", 
    "html": "https://aperta.ulakbim.gov.tr/record/271298", 
    "latest": "https://aperta.ulakbim.gov.tr/api/records/271298", 
    "latest_html": "https://aperta.ulakbim.gov.tr/record/271298"
  }, 
  "metadata": {
    "access_right": "open", 
    "access_right_category": "success", 
    "communities": [
      {
        "id": "tubitak-destekli-proje-yayinlari"
      }
    ], 
    "creators": [
      {
        "affiliation": "Univ Toulouse III Paul Sabatier UT3, CNRS, Inst Pharmacol & Biol Struct IPBS, F-31077 Toulouse, France", 
        "name": "Altiner, Pinar"
      }, 
      {
        "affiliation": "Univ Oxford, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England", 
        "name": "Cinaroglu, Suleyman Selim"
      }, 
      {
        "affiliation": "Acibadem Univ, Fac Engn & Nat Sci, Dept Mol Biol & Genet, TR-34752 Istanbul, Turkiye", 
        "name": "Timucin, Ahmet Can"
      }, 
      {
        "affiliation": "Acibadem Univ, Sch Med, Dept Biostat & Med Informat, TR-34752 Istanbul, Turkiye", 
        "name": "Timucin, Emel"
      }
    ], 
    "description": "<p>Inhibiting protein-protein interactions of the Myc family is a viable pharmacological strategy for modulation of the levels of Myc oncoproteins in cancer. Aurora A kinase (AurA) and N-Myc interaction is one of the most attractive targets of this strategy because formation of this complex blocks proteasomal degradation of N-Myc in neuroblastoma. Two crystallization studies have captured this complex (PDB IDs: 5g1x, 7ztl), partially resolving the AurA interaction region (AIR) of N-Myc. Prompted by the missing N-Myc fragment in these crystal structures, we modeled the complete structure between AurA and N-Myc, and comprehensively analyzed how the incomplete and complete N-Myc behave in complex by molecular dynamics simulations. Molecular dynamics simulations of the incomplete PDB complex (5g1x) repeatedly showed partial dissociation of the short N-Myc fragment (61-89) from the kinase. The missing N-Myc (19-60) fragment was modeled utilizing the N-terminal lobe of AurA as the protein-protein interaction surface, wherein TPX2, a well-known partner of AurA, also binds. Binding free energy calculations along with flexibility analysis confirmed that the complete AIR of N-Myc stabilizes the complex, accentuating the N-terminal lobe of AurA as a binding site for the missing N-Myc fragment (19-60). We further generated additional models consisting of only the missing N-Myc (19-60), and the fused form of TPX2 (7-43) and N-Myc (61-89). These partners also formed more stable interactions with the N-terminal lobe of AurA than did the incomplete N-Myc fragment (61-89) in the 5g1x complex. Altogether, this study provides structural insights into the involvement of the N-terminus of the AIR of N-Myc and the N-terminal lobe of AurA in formation of a stable complex, reflecting its potential for effective targeting of N-Myc.</p>", 
    "doi": "10.1038/s41598-023-45272-3", 
    "has_grant": false, 
    "journal": {
      "issue": "1", 
      "pages": "15", 
      "title": "SCIENTIFIC REPORTS", 
      "volume": "13"
    }, 
    "license": {
      "id": "cc-by"
    }, 
    "publication_date": "2023-01-01", 
    "relations": {
      "version": [
        {
          "count": 1, 
          "index": 0, 
          "is_last": true, 
          "last_child": {
            "pid_type": "recid", 
            "pid_value": "271298"
          }, 
          "parent": {
            "pid_type": "recid", 
            "pid_value": "271297"
          }
        }
      ]
    }, 
    "resource_type": {
      "subtype": "article", 
      "title": "Dergi makalesi", 
      "type": "publication"
    }, 
    "science_branches": [
      "Di\u011fer"
    ], 
    "title": "Computational completion of the Aurora interaction region of N-Myc in the Aurora a kinase complex"
  }, 
  "owners": [
    1
  ], 
  "revision": 1, 
  "stats": {
    "downloads": 3.0, 
    "unique_downloads": 3.0, 
    "unique_views": 18.0, 
    "version_downloads": 3.0, 
    "version_unique_downloads": 3.0, 
    "version_unique_views": 18.0, 
    "version_views": 18.0, 
    "version_volume": 597.0, 
    "views": 18.0, 
    "volume": 597.0
  }, 
  "updated": "2024-06-07T16:32:39.136653+00:00"
}