Crystal Structure of IMP-2 Metallo-β-lactamase from <i>Acinetobacter</i> spp.

• Yamaguchi Yoshihiro

  Environmental Safety Center, Kumamoto University

• Matsueda Satoshi

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• Matsunaga Kazuyo

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• Takashio Nobutoshi

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• Toma-Fukai Sachiko

  Graduate School of Pharmaceutical Sciences, The University of Tokyo

• Yamagata Yuriko

  Graduate School of Pharmaceutical Sciences, Kumamoto University

• Shibata Naohiro

  Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases

• Wachino Jun-ichi

  Department of Bacteriology, Nagoya University Graduate School of Medicine

• Shibayama Keigo

  Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases

• Arakawa Yoshichika

  Department of Bacteriology, Nagoya University Graduate School of Medicine

• Kurosaki Hiromasa

  Graduate School of Pharmaceutical Sciences, Kumamoto University

Bibliographic Information

Other Title

• Crystal Structure of IMP-2 Metallo-β-lactamase from Acinetobacter spp. : Comparison of Active-Site Loop Structures between IMP-1 and IMP-2
• Crystal Structure of IMP-2 Metallo-β-lactamase from Acinetobacter spp.
• Comparison of Active-Site Loop Structures between IMP-1 and IMP-2

Abstract

IMP-2, a subclass B1 metallo-β-lactamase (MBL), is a Zn(II)-containing hydrolase. This hydrolase, involved in antibiotic resistance, catalyzes the hydrolysis of the C–N bond of the β-lactam ring in β-lactam antibiotics such as benzylpenicillin and imipenem. The crystal structure of IMP-2 MBL from Acinetobacter spp. was determined at 2.3 Å resolution. This structure is analogous to that of subclass B1 MBLs such as IMP-1 and VIM-2. Comparison of the structures of IMP-1 and IMP-2, which have an 85% amino acid identity, suggests that the amino acid substitution at position 68 on a β-strand (β3) (Pro in IMP-1 versus Ser in IMP-2) may be a staple factor affecting the flexibility of loop 1 (comprising residues at positions 60–66; EVNGWGV). In the IMP-1 structure, loop 1 adopts an open, disordered conformation. On the other hand, loop 1 of IMP-2 forms a closed conformation in which the side chain of Trp64, involved in substrate binding, is oriented so as to cover the active site, even though there is an acetate ion in the active site of both IMP-1 and IMP-2. Loop 1 of IMP-2 has a more flexible structure in comparison to IMP-1 due to having a Ser residue instead of the Pro residue at position 68, indicating that this difference in sequence may be a trigger to induce a more flexible conformation in loop 1.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 38 (1), 96-101, 2015

  The Pharmaceutical Society of Japan

Keywords

• antibiotic resistance
• β-lactam antibiotic
• metallo-β-lactamase
• X-ray crystallography

Details

• CRID: 1390001204631182592
• NII Article ID: 130004872220
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b14-00594
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 026001010
• PubMed: 25744464
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026001010
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/1/38_b14-00594/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015261405
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed