4Y68

Structure of a lipoprotein from Streptococcus agalactiae

Summary for 4Y68

• Entry DOI: 10.2210/pdb4y68/pdb
• Descriptor: Putative nisin-resistance protein, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: lipoprotein, lantibiotic, peptidase, hydrolase
• Biological source: Streptococcus agalactiae 515
• Total number of polymer chains: 4
• Total formula weight: 142606.73

Authors

Khosa, S.,Hoeppner, A.,Smits, S.H. (deposition date: 2015-02-12, release date: 2016-01-20, Last modification date: 2024-05-08)

Primary citation

Khosa, S.,Frieg, B.,Mulnaes, D.,Kleinschrodt, D.,Hoeppner, A.,Gohlke, H.,Smits, S.H.
Structural basis of lantibiotic recognition by the nisin resistance protein from Streptococcus agalactiae.
Sci Rep, 6:18679-18679, 2016

PubMed Abstract: Lantibiotics are potent antimicrobial peptides. Nisin is the most prominent member and contains five crucial lanthionine rings. Some clinically relevant bacteria express membrane-associated resistance proteins that proteolytically inactivate nisin. However, substrate recognition and specificity of these proteins is unknown. Here, we report the first three-dimensional structure of a nisin resistance protein from Streptococcus agalactiae (SaNSR) at 2.2 Å resolution. It contains an N-terminal helical bundle, and protease cap and core domains. The latter harbors the highly conserved TASSAEM region, which lies in a hydrophobic tunnel formed by all domains. By integrative modeling, mutagenesis studies, and genetic engineering of nisin variants, a model of the SaNSR/nisin complex is generated, revealing that SaNSR recognizes the last C-terminally located lanthionine ring of nisin. This determines the substrate specificity of SaNSR and ensures the exact coordination of the nisin cleavage site at the TASSAEM region.

PubMed: 26727488
DOI: 10.1038/srep18679

Experimental method

X-RAY DIFFRACTION (2.21 Å)