Structural, kinetic, and evolutionary peculiarities of HISN3, a plant 5'-ProFAR isomerase.
Plant Physiol Biochem
; 215: 109065, 2024 Aug 22.
Article
en En
| MEDLINE
| ID: mdl-39186852
ABSTRACT
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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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Plant Physiol Biochem
Asunto de la revista:
BIOQUIMICA
/
BOTANICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Polonia