3ZMH

Structure of E.coli rhomboid protease GlpG in complex with monobactam L62

Summary for 3ZMH

• Entry DOI: 10.2210/pdb3zmh/pdb
• Related: 3ZMI 3ZMJ 3ZOT
• Descriptor: RHOMBOID PROTEASE GLPG, cyclopentyl N-[(1R)-3-oxidanylidene-1-phenyl-propyl]carbamate, CYCLOPENTYL 2-OXO-4-PHENYLAZETIDINE-1-CARBOXYLATE, ... (6 entities in total)
• Functional Keywords: hydrolase, intra-membrane protease, acyl enzyme, beta lactams, anitbiotic
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 22773.02

Authors

Vinothkumar, K.R.,Pierrat, O.A.,Large, J.M.,Freeman, M. (deposition date: 2013-02-11, release date: 2013-05-22, Last modification date: 2024-10-16)

Primary citation

Vinothkumar, K.R.,Pierrat, O.A.,Large, J.M.,Freeman, M.
Structure of rhomboid protease in complex with beta-lactam inhibitors defines the S2' cavity.
Structure, 21:1051-1058, 2013

PubMed Abstract: Rhomboids are evolutionarily conserved serine proteases that cleave transmembrane proteins within the membrane. The increasing number of known rhomboid functions in prokaryotes and eukaryotes makes them attractive drug targets. Here, we describe structures of the Escherichia coli rhomboid GlpG in complex with β-lactam inhibitors. The inhibitors form a single bond to the catalytic serine and the carbonyl oxygen of the inhibitor faces away from the oxyanion hole. The hydrophobic N-substituent of β-lactam inhibitors points into a cavity within the enzyme, providing a structural explanation for the specificity of β-lactams on rhomboid proteases. This same cavity probably represents the S2' substrate binding site of GlpG. We suggest that the structural changes in β-lactam inhibitor binding reflect the state of the enzyme at an initial stage of substrate binding to the active site. The structural insights from these enzyme-inhibitor complexes provide a starting point for structure-based design for rhomboid inhibitors.

PubMed: 23665170
DOI: 10.1016/j.str.2013.03.013

Experimental method

X-RAY DIFFRACTION (2.3 Å)