3ITA

Crystal structure of Penicillin-Binding Protein 6 (PBP6) from E. coli in acyl-enzyme complex with ampicillin

Summary for 3ITA

• Entry DOI: 10.2210/pdb3ita/pdb
• Related: 3IT9 3ITB
• Descriptor: D-alanyl-D-alanine carboxypeptidase dacC, (2R,4S)-2-[(1R)-1-{[(2R)-2-amino-2-phenylacetyl]amino}-2-oxoethyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ppenicillin-binding protein, bp6, dd-carboxypeptidase, peptidoglycan, ampicillin, acyl-enzyme complex, carboxypeptidase, cell inner membrane, cell membrane, cell shape, cell wall biogenesis/degradation, hydrolase, membrane, peptidoglycan synthesis, protease
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane ; Peripheral membrane protein ; Periplasmic side : P08506
• Total number of polymer chains: 4
• Total formula weight: 153642.41

Authors

Chen, Y.,Zhang, W.,Shi, Q.,Hesek, D.,Lee, M.,Mobashery, S.,Shoichet, B.K. (deposition date: 2009-08-27, release date: 2009-10-20, Last modification date: 2024-04-03)

Primary citation

Chen, Y.,Zhang, W.,Shi, Q.,Hesek, D.,Lee, M.,Mobashery, S.,Shoichet, B.K.
Crystal structures of penicillin-binding protein 6 from Escherichia coli.
J.Am.Chem.Soc., 131:14345-14354, 2009

PubMed Abstract: Penicillin-binding protein 6 (PBP6) is one of the two main DD-carboxypeptidases in Escherichia coli, which are implicated in maturation of bacterial cell wall and formation of cell shape. Here, we report the first X-ray crystal structures of PBP6, capturing its apo state (2.1 A), an acyl-enzyme intermediate with the antibiotic ampicillin (1.8 A), and for the first time for a PBP, a preacylation complex (a "Michaelis complex", determined at 1.8 A) with a peptidoglycan substrate fragment containing the full pentapeptide, NAM-(L-Ala-D-isoGlu-L-Lys-D-Ala-D-Ala). These structures illuminate the molecular interactions essential for ligand recognition and catalysis by DD-carboxypeptidases, and suggest a coupling of conformational flexibility of active site loops to the reaction coordinate. The substrate fragment complex structure, in particular, provides templates for models of cell wall recognition by PBPs, as well as substantiating evidence for the molecular mimicry by beta-lactam antibiotics of the peptidoglycan acyl-D-Ala-D-Ala moiety.

PubMed: 19807181
DOI: 10.1021/ja903773f

Experimental method

X-RAY DIFFRACTION (1.8 Å)