Cell wall branches, penicillin resistance and the secrets of the MurM protein.
Production of low-affinity forms of penicillin-binding proteins (PBPs), although essential, is not sufficient to protect pneumococci against the inhibitory action of penicillin. Resistance also requires the newly identified protein MurM which, together with MurN, is involved with the synthesis of short peptide branches in the pneumococcal cell wall. Cells in which murM was inactivated produced cell walls without branches and also completely lost penicillin resistance. To understand these surprising observations a 3D-model of MurM was constructed, which helped to put into structural context several of the biochemical and genetic observations made about this protein.
Fiser
András
A
Department of Biochemistry and Seaver Foundation Center for Bioinformatics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Filipe
Sergio R
SR
Tomasz
Alexander
A
D001419:Bacteria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D006602:Hexosyltransferases / Q000502:physiology; D008958:Models, Molecular; D002267:Muramoylpentapeptide Carboxypeptidase / Q000502:physiology; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010453:Peptide Synthases / Q000737:chemistry* / Q000502:physiology*; D010457:Peptidoglycan / Q000096:biosynthesis*; D010458:Peptidyl Transferases / Q000502:physiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; C408066:MurM protein, Streptococcus pneumoniae; C408067:MurN protein, Streptococcus pneumoniae; D010453:Peptide Synthases