Structural, kinetic, and evolutionary peculiarities of HISN3, a plant 5'-ProFAR isomerase
Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
| Veröffentlicht in: | Plant physiology and biochemistry : PPB. - 1991. - 215(2024) vom: 15. Sept., Seite 109065 |
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| Weitere Verfasser: | , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Plant physiology and biochemistry : PPB |
| Schlagworte: | Journal Article (βα)(8)-barrel Herbicide resistance Histidine biosynthesis PriA TIM barrel TrpF Plant Proteins Isomerases EC 5.- mehr... |
| Zusammenfassung: | Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved. Histidine biosynthesis is essential for the growth and development of plants, where it occurs within chloroplasts. The eleven reactions are catalyzed by eight enzymes, known as HISN1-8, each acting sequentially. Here, we present the crystal structures of a 5'-ProFAR isomerase (HISN3) from the model legume Medicago truncatula bound to its enzymatically synthesized substrate (ProFAR) and product (PrFAR). The active site of MtHISN3 contains a sodium cation that participates in ligand recognition, a feature not observed in bacterial and fungal structures of homologous enzymes. The steady-state kinetics of wild-type MtHISN3 revealed a slightly higher turnover rate compared to its bacterial homologs. Plant HISN3 sequences contain an unusually elongated Lys60-Ser91 fragment, while deletion of the 74-80 region resulted in a 30-fold loss in catalytic efficiency compared to the wild-type. Molecular dynamics simulations suggested that the fragment facilitates product release, thereby contributing to a higher kcat. Moreover, conservation analyses suggested a non-cyanobacterial origin for plant HISN3 enzymes, which is another instance of a non-cyanobacterial enzyme in the plant histidine biosynthetic pathway. Finally, a virtual screening campaign yielded five molecules, with the energy gains ranging between -13.6 and -13.1 kcal/mol, which provide new scaffolds for the future development of herbicides |
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| Beschreibung: | Date Completed 14.09.2024 Date Revised 17.09.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1873-2690 |
| DOI: | 10.1016/j.plaphy.2024.109065 |