8WU7

Structure of a cis-Geranylfarnesyl Diphosphate Synthase from Streptomyces clavuligerus

Summary for 8WU7

• Entry DOI: 10.2210/pdb8wu7/pdb
• Descriptor: Isoprenyl transferase (2 entities in total)
• Functional Keywords: cis-prenyltransferase, biosynthetic protein
• Biological source: Streptomyces clavuligerus
• Total number of polymer chains: 1
• Total formula weight: 32477.70

Authors

Li, F.R.,Wang, Q.L.,Pan, X.M.,Dong, L.B. (deposition date: 2023-10-20, release date: 2024-05-08, Last modification date: 2024-07-10)

Primary citation

Li, F.R.,Wang, Q.,Pan, X.,Xu, H.M.,Dong, L.B.
Discovery, Structure, and Engineering of a cis-Geranylfarnesyl Diphosphate Synthase.
Angew.Chem.Int.Ed.Engl., 63:e202401669-e202401669, 2024

PubMed Abstract: cis-Prenyltransferases (cis-PTs) catalyze the sequential head-to-tail condensation of isopentenyl diphosphate (IPP) to allylic diphosphates, producing mixed E-Z prenyl diphosphates of varying lengths; however, the specific enzymes synthesizing cis-C prenyl diphosphates have not been identified. Herein, we present the discovery and characterization of a cis-geranylfarnesyl diphosphate synthase (ScGFPPS) from Streptomyces clavuligerus. This enzyme demonstrates high catalytic proficiency in generating six distinct cis-polyisoprenoids, including three C and three C variants. We determined the crystal structure of ScGFPPS. Additionally, we unveil the crystal structure of nerylneryl diphosphate synthase (NNPS), known for synthesizing an all-cis-C polyisoprenoid. Comparative structural analysis of ScGFPPS and NNPS has identified key differences that influence product specificity. Through site-directed mutagenesis, we have identified eight single mutations that significantly refine the selectivity of ScGFPPS for cis-polyisoprenoids. Our findings not only expand the functional spectrum of cis-PTs but also provide a structural comparison strategy in cis-PTs engineering.

PubMed: 38651244
DOI: 10.1002/anie.202401669

Experimental method

X-RAY DIFFRACTION (2.09 Å)