9HP7
Crystal structure of GH19 E228Q domain of D29-LysA in complex with (GlcNAc)4
Summary for 9HP7
| Entry DOI | 10.2210/pdb9hp7/pdb |
| Descriptor | Endolysin A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | peptidoglycan hydrolase, d29-lysa, gh19, (glcnac)4, hydrolase |
| Biological source | Mycobacterium phage D29 |
| Total number of polymer chains | 1 |
| Total formula weight | 22513.03 |
| Authors | |
| Primary citation | Ceballos-Zuniga, F.,Galvez-Larrosa, L.,Munoz, I.G.,Infantes, L.,Fernandez-Carrillo, J.,Perez-Dorado, I. Dissecting the molecular basis underlying mycobacterial cell-wall hydrolysis by the catalytic domains of D29LysA and DS6ALysA phage endolysins. Int.J.Biol.Macromol., 334:148896-148896, 2025 Cited by PubMed Abstract: Mycobacterial infections, including tuberculosis, remain a major global health challenge, causing millions of deaths annually. Their treatment is increasingly hindered by limited therapeutic options and rising antimicrobial resistance, highlighting the urgent need for alternative strategies. Mycobacteriophage LysA endolysins are complex multi-domain peptidoglycan hydrolases emerging as potential tools to treat mycobacterial infections. However, despite the therapeutic prospects of LysAs, our understanding of their mechanism of action remains limited. This study provides a comprehensive structural-functional analysis of the catalytic domains of D29LysA and DS6ALysA endolysins (D29N4/D29GH19 and DS6AGH19/DS6AAmi2B), characterised alone and in complex with PG analogues, using protein engineering, X-ray crystallography, small-angle X-ray scattering, and in silico tools. Our results reveal precise details of the substrate-binding site and the catalytic platforms at each domain, including information about substrate-binding mode and conformational changes associated with peptidoglycan recognition and hydrolysis. Moreover, these findings also suggest a coordinated mechanism of action of both catalytic domains in DS6ALysA lysin. These insights represent a significant advance in understanding the structural basis of mycobacterial cell-wall degradation by mycobacteriophage endolysins. Information that may aid in further exploring these endolysins as therapeutic antimicrobial tools in the future. PubMed: 41207583DOI: 10.1016/j.ijbiomac.2025.148896 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.83 Å) |
Structure validation
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