8I8H

Crystal structure of Cph001-D189N in complex with VIO and ATP

Summary for 8I8H

• Entry DOI: 10.2210/pdb8i8h/pdb
• Related PRD ID: PRD_000226
• Descriptor: Viomycin kinase, KBE-DPP-SER-SER-UAL-5OH, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: phosphotransferase, capreomycin, cph, resistance, transferase, atp, viomycin
• Biological source: Streptosporangium roseum; More
• Total number of polymer chains: 3
• Total formula weight: 62194.23

Authors

Chang, C.Y.,Toh, S.I.,Elaine K, J.,Hsiao, P.Y. (deposition date: 2023-02-04, release date: 2024-01-10)

Primary citation

Toh, S.I.,Elaine Keisha, J.,Wang, Y.L.,Pan, Y.C.,Jhu, Y.H.,Hsiao, P.Y.,Liao, W.T.,Chen, P.Y.,Ko, T.M.,Chang, C.Y.
Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin.
Commun Biol, 6:1282-1282, 2023

PubMed Abstract: Metagenomic-based studies have predicted an extraordinary number of potential antibiotic-resistance genes (ARGs). These ARGs are hidden in various environmental bacteria and may become a latent crisis for antibiotic therapy via horizontal gene transfer. In this study, we focus on a resistance gene cph, which encodes a phosphotransferase (Cph) that confers resistance to the antituberculosis drug capreomycin (CMN). Sequence Similarity Network (SSN) analysis classified 353 Cph homologues into five major clusters, where the proteins in cluster I were found in a broad range of actinobacteria. We examine the function and antibiotics targeted by three putative resistance proteins in cluster I via biochemical and protein structural analysis. Our findings reveal that these three proteins in cluster I confer resistance to CMN, highlighting an important aspect of CMN resistance within this gene family. This study contributes towards understanding the sequence-structure-function relationships of the phosphorylation resistance genes that confer resistance to CMN.

PubMed: 38114770
DOI: 10.1038/s42003-023-05681-6

Experimental method

X-RAY DIFFRACTION (2.02 Å)