2DQM

Crystal Structure of Aminopeptidase N complexed with bestatin

Summary for 2DQM

• Entry DOI: 10.2210/pdb2dqm/pdb
• Related: 2DQ6
• Descriptor: Aminopeptidase N, ZINC ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: clan ma, family m1, gluzincin metallopeptidase, inhibitor complex, hydrolase
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Peripheral membrane protein; Cytoplasmic side: P04825
• Total number of polymer chains: 1
• Total formula weight: 99594.55

Authors

Onohara, Y.,Nakajima, Y.,Ito, K.,Yoshimoto, T. (deposition date: 2006-05-29, release date: 2006-08-01, Last modification date: 2023-10-25)

Primary citation

Ito, K.,Nakajima, Y.,Onohara, Y.,Takeo, M.,Nakashima, K.,Matsubara, F.,Ito, T.,Yoshimoto, T.
Aminopeptidase N (proteobacteria alanyl aminopeptidase) from Escherichia coli: Crystal structure and conformational change of the methionine 260 residue involved in substrate recognition
J.Biol.Chem., 281:33664-33676, 2006

PubMed Abstract: Aminopeptidase N from Escherichia coli is a broad specificity zinc exopeptidase belonging to aminopeptidase clan MA, family M1. The structures of the ligand-free form and the enzyme-bestatin complex were determined at 1.5- and 1.6-A resolution, respectively. The enzyme is composed of four domains: an N-terminal beta-domain (Met(1)-Asp(193)), a catalytic domain (Phe(194)-Gly(444)), a middle beta-domain (Thr(445)-Trp(546)), and a C-terminal alpha-domain (Ser(547)-Ala(870)). The structure of the catalytic domain exhibits similarity to thermolysin, and a metal-binding motif (HEXXHX(18)E) is found in the domain. The zinc ion is coordinated by His(297), His(301), Glu(320), and a water molecule. The groove on the catalytic domain that contains the active site is covered by the C-terminal alpha-domain, and a large cavity is formed inside the protein. However, there exists a small hole at the center of the C-terminal alpha-domain. The N terminus of bestatin is recognized by Glu(121) and Glu(264), which are located in the N-terminal and catalytic domains, respectively. Glu(298) and Tyr(381), located near the zinc ion, are considered to be involved in peptide cleavage. A difference revealed between the ligand-free form and the enzyme-bestatin complex indicated that Met(260) functions as a cushion to accept substrates with different N-terminal residue sizes, resulting in the broad substrate specificity of this enzyme.

PubMed: 16885166
DOI: 10.1074/jbc.M605203200

Experimental method

X-RAY DIFFRACTION (1.6 Å)