Activation by Allostery in Cell-Wall Remodeling by a Modular Membrane-Bound Lytic Transglycosylase from Pseudomonas aeruginosa.
Bacteria grow and divide without loss of cellular integrity. This accomplishment is notable, as a key component of their cell envelope is a surrounding glycopeptide polymer. In Gram-negative bacteria this polymer-the peptidoglycan-grows by the difference between concurrent synthesis and degradation. The regulation of the enzymatic ensemble for these activities is poorly understood. We report herein the structural basis for the control of one such enzyme, the lytic transglycosylase MltF of Pseudomonas aeruginosa. Its structure comprises two modules: an ABC-transporter-like regulatory module and a catalytic module. Occupancy of the regulatory module by peptidoglycan-derived muropeptides effects a dramatic and long-distance (40 Å) conformational change, occurring over the entire protein structure, to open its active site for catalysis. This discovery of the molecular basis for the allosteric control of MltF catalysis is foundational to further study of MltF within the complex enzymatic orchestration of the dynamic peptidoglycan.
Departamento de Cristalografía y Biología Estructural, Instituto de Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain.
Teresa
T
Domínguez-Gil
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Mijoon
M
Lee
Departamento de Cristalografía y Biología Estructural, Instituto de Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain.
Iván
I
Acebrón-Avalos
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Kiran V
KV
Mahasenan
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Dusan
D
Hesek
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
David A
DA
Dik
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Byungjin
B
Byun
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Elena
E
Lastochkin
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Jed F
JF
Fisher
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: mobashery@nd.edu.
Shahriar
S
Mobashery
Departamento de Cristalografía y Biología Estructural, Instituto de Química-Física "Rocasolano", CSIC, Serrano 119, 28006 Madrid, Spain. Electronic address: xjuan@iqfr.csic.es.
Juan A
JA
Hermoso
D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002473:Cell Wall / Q000378:metabolism; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D016695:Glycosyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D010457:Peptidoglycan / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000201:enzymology*
D001426:Bacterial Proteins; D010457:Peptidoglycan; D016695:Glycosyltransferases