8XYF

Crystal structure of Holo-PlyGRCS, a bacteriophage Endolysin in complex with Cold shock protein C

Summary for 8XYF

• Entry DOI: 10.2210/pdb8xyf/pdb
• Descriptor: Endolysin, Cold shock-like protein CspC, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: peptidoglycan hydrolase, cold shock protein, lytic activity, antimicrobial protein
• Biological source: Staphylococcus phage GRCS; More
• Total number of polymer chains: 2
• Total formula weight: 36984.06

Authors

Padmanabhan, B.,Gopinath, K.,Harshitha, H.N. (deposition date: 2024-01-19, release date: 2025-01-01, Last modification date: 2025-03-19)

Primary citation

Krishnappa, G.,Nagaraj, H.,SureshKumar, H.B.,Mandal, M.,Padavattan, S.,Bahubali, V.H.,Thiyagarajan, S.,Padmanabhan, B.
Structural Basis for the Essential Role of Ca 2+ in the Lytic Activity of Staphylococcus aureus PlyGRCS Endolysin Targeting Methicillin-Resistant Staphylococcus aureus.
Proteins, 93:920-933, 2025

PubMed Abstract: Staphylococcus aureus causes a wide range of infections, from mild skin conditions to severe, life-threatening diseases. Bacteriophage endolysins exhibit a selective capacity to degrade the peptidoglycan layer of Gram-positive bacteria, making promising biotherapeutic agents against antibiotic-resistant infections. PlyGRCS, a specific endolysin derived from S. aureus, comprises a catalytic CHAP domain and a cell-wall binding SH3_5 domain connected by a linker. Ca ions are essential for the CHAP domain's catalytic function. The crystal structure of PlyGRCS, determined in the absence of Ca and refined to a resolution of 1.67 Å, revealed significant conformational changes in the Ca binding site. Antimicrobial assays with Ca-deficient PlyGRCS and mutants targeting key residues in the catalytic and Ca binding regions highlighted the importance of specific functional residues for lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). These structural and microbial studies provide valuable insights into the critical residues contributing to PlyGRCS's bacteriolytic efficacy against MRSA.

PubMed: 39660753
DOI: 10.1002/prot.26777

Experimental method

X-RAY DIFFRACTION (1.67 Å)