Homoprotocatechuate dioxygenase active site: Imitating the secondary sphere base via computational design

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BÜYÜKTEMİZ M., DEDE Y.

Turkish Journal of Chemistry, cilt.47, sa.5, ss.1116-1124, 2023 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 47 Sayı: 5
  • Basım Tarihi: 2023
  • Doi Numarası: 10.55730/1300-0527.3598
  • Dergi Adı: Turkish Journal of Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.1116-1124
  • Anahtar Kelimeler: dioxygenase, Enzyme active site, homoprotocatechuate dioxygenase, proton transfer, secondary sphere
  • Gazi Üniversitesi Adresli: Evet

Özet

Oxidative ring cleavage reactions have attracted great interest and various studies on the catechol ring-cleaving enzyme homoprotocatechuate dioxygenase (HPCD) have been reported in the literature. The available data on how the proton transfer takes place led us to design a potential HPCD model structure. A secondary sphere effect of utmost importance, the assistance of His200, which is critical for the catechol proton to migrate to dioxygen, was cautiously included on the first coordination shell. This was done mainly by modifying the axial ligands in the first coordination shell of HPCD such that the dual basic/acidic role in the proton transfer pathway of His200 was reproduced. Model systems with mono-, bi-, and tridentate ligands are reported. Energetically feasible reaction channels on synthetically promising ligand structures are identified. Key structural and electronic principles for obtaining viable proton transfer paths are outlined.