This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1c3b
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1c3b.gif|left|200px]] | + | [[Image:1c3b.gif|left|200px]] |
| - | + | ||
| - | '''AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR, BENZO(B)THIOPHENE-2-BORONIC ACID (BZB)''' | + | {{Structure |
| + | |PDB= 1c3b |SIZE=350|CAPTION= <scene name='initialview01'>1c3b</scene>, resolution 2.25Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=BZB:BENZO[B]THIOPHENE-2-BORONIC ACID'>BZB</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR, BENZO(B)THIOPHENE-2-BORONIC ACID (BZB)''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1C3B is a [ | + | 1C3B is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3B OCA]. |
==Reference== | ==Reference== | ||
| - | The complexed structure and antimicrobial activity of a non-beta-lactam inhibitor of AmpC beta-lactamase., Powers RA, Blazquez J, Weston GS, Morosini MI, Baquero F, Shoichet BK, Protein Sci. 1999 Nov;8(11):2330-7. PMID:[http:// | + | The complexed structure and antimicrobial activity of a non-beta-lactam inhibitor of AmpC beta-lactamase., Powers RA, Blazquez J, Weston GS, Morosini MI, Baquero F, Shoichet BK, Protein Sci. 1999 Nov;8(11):2330-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10595535 10595535] |
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
| Line 25: | Line 34: | ||
[[Category: serine hydrolase]] | [[Category: serine hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:19:14 2008'' |
Revision as of 08:19, 20 March 2008
| |||||||
| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR, BENZO(B)THIOPHENE-2-BORONIC ACID (BZB)
Overview
Beta-lactamases are the major resistance mechanism to beta-lactam antibiotics and pose a growing threat to public health. Recently, bacteria have become resistant to beta-lactamase inhibitors, making this problem pressing. In an effort to overcome this resistance, non-beta-lactam inhibitors of beta-lactamases were investigated for complementarity to the structure of AmpC beta-lactamase from Escherichia coli. This led to the discovery of an inhibitor, benzo(b)thiophene-2-boronic acid (BZBTH2B), which inhibited AmpC with a Ki of 27 nM. This inhibitor is chemically dissimilar to beta-lactams, raising the question of what specific interactions are responsible for its activity. To answer this question, the X-ray crystallographic structure of BZBTH2B in complex with AmpC was determined to 2.25 A resolution. The structure reveals several unexpected interactions. The inhibitor appears to complement the conserved, R1-amide binding region of AmpC, despite lacking an amide group. Interactions between one of the boronic acid oxygen atoms, Tyr150, and an ordered water molecule suggest a mechanism for acid/base catalysis and a direction for hydrolytic attack in the enzyme catalyzed reaction. To investigate how a non-beta-lactam inhibitor would perform against resistant bacteria, BZBTH2B was tested in antimicrobial assays. BZBTH2B significantly potentiated the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria. This inhibitor was unaffected by two common resistance mechanisms that often arise against beta-lactams in conjunction with beta-lactamases. Porin channel mutations did not decrease the efficacy of BZBTH2B against cells expressing AmpC. Also, this inhibitor did not induce expression of AmpC, a problem with many beta-lactams. The structure of the BZBTH2B/AmpC complex provides a starting point for the structure-based elaboration of this class of non-beta-lactam inhibitors.
About this Structure
1C3B is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
The complexed structure and antimicrobial activity of a non-beta-lactam inhibitor of AmpC beta-lactamase., Powers RA, Blazquez J, Weston GS, Morosini MI, Baquero F, Shoichet BK, Protein Sci. 1999 Nov;8(11):2330-7. PMID:10595535
Page seeded by OCA on Thu Mar 20 10:19:14 2008
