9FCG
Medicago truncatula 5'-ProFAR isomerase (HISN3) D57N mutant in complex with PrFAR
Summary for 9FCG
| Entry DOI | 10.2210/pdb9fcg/pdb |
| Descriptor | 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase, chloroplastic, [(2R,3S,4R,5R)-5-[4-AMINOCARBONYL-5-[[(Z)-[(3R,4R)-3,4-DIHYDROXY-2-OXO-5-PHOSPHONOOXY-PENTYL]IMINOMETHYL]AMINO]IMIDAZOL-1-YL]-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL DIHYDROGEN PHOSPHATE, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (6 entities in total) |
| Functional Keywords | complex, product, side-product, bbm ii isomerase, histidine biosynthesis, hisa, isomerase |
| Biological source | Medicago truncatula (barrel medic) |
| Total number of polymer chains | 1 |
| Total formula weight | 31336.76 |
| Authors | |
| Primary citation | Witek, W.,Imiolczyk, B.,Ruszkowski, M. Structural, kinetic, and evolutionary peculiarities of HISN3, a plant 5'-ProFAR isomerase. Plant Physiol Biochem., 215:109065-109065, 2024 Cited by PubMed 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 k. 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. PubMed: 39186852DOI: 10.1016/j.plaphy.2024.109065 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.54 Å) |
Structure validation
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