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.
1dy6
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | The structure of the beta-lactamase SME-1 from Serratia marcescens, a | + | The structure of the beta-lactamase SME-1 from Serratia marcescens, a class A enzyme characterized by its significant activity against imipenem, has been determined to 2.13 A resolution. The overall structure of SME-1 is similar to that of other class A beta-lactamases. In the active-site cavity, most of the residues found in SME-1 are conserved among class A beta-lactamases, except at positions 104, 105 and 237, where a tyrosine, a histidine and a serine are found, respectively, and at position 238, which is occupied by a cysteine forming a disulfide bridge with the other cysteine residue located at position 69. The crucial role played by this disulfide bridge in SME-1 was confirmed by site-directed mutagenesis of Cys69 to Ala, which resulted in a mutant unable to confer resistance to imipenem and all other beta-lactam antibiotics tested. Another striking structural feature found in SME-1 was the short distance separating the side chains of the active serine residue at position 70 and the strictly conserved glutamate at position 166, which is up to 1.4 A shorter in SME-1 compared with other class A beta-lactamases. Consequently, the SME-1 structure cannot accommodate the essential catalytic water molecule found between Ser70 and Glu166 in the other class A beta-lactamases described so far, suggesting that a significant conformational change may be necessary in SME-1 to properly position the hydrolytic water molecule involved in the hydrolysis of the acyl-enzyme intermediate. |
==About this Structure== | ==About this Structure== | ||
| Line 17: | Line 17: | ||
[[Category: Delettre, J.]] | [[Category: Delettre, J.]] | ||
[[Category: Guillet, V.]] | [[Category: Guillet, V.]] | ||
| - | [[Category: Hermite, G | + | [[Category: Hermite, G L.]] |
[[Category: Jarlier, V.]] | [[Category: Jarlier, V.]] | ||
[[Category: Naas, T.]] | [[Category: Naas, T.]] | ||
| Line 28: | Line 28: | ||
[[Category: lactamase]] | [[Category: lactamase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:21:48 2008'' |
Revision as of 10:21, 21 February 2008
|
STRUCTURE OF THE IMIPENEM-HYDROLYZING BETA-LACTAMASE SME-1
Overview
The structure of the beta-lactamase SME-1 from Serratia marcescens, a class A enzyme characterized by its significant activity against imipenem, has been determined to 2.13 A resolution. The overall structure of SME-1 is similar to that of other class A beta-lactamases. In the active-site cavity, most of the residues found in SME-1 are conserved among class A beta-lactamases, except at positions 104, 105 and 237, where a tyrosine, a histidine and a serine are found, respectively, and at position 238, which is occupied by a cysteine forming a disulfide bridge with the other cysteine residue located at position 69. The crucial role played by this disulfide bridge in SME-1 was confirmed by site-directed mutagenesis of Cys69 to Ala, which resulted in a mutant unable to confer resistance to imipenem and all other beta-lactam antibiotics tested. Another striking structural feature found in SME-1 was the short distance separating the side chains of the active serine residue at position 70 and the strictly conserved glutamate at position 166, which is up to 1.4 A shorter in SME-1 compared with other class A beta-lactamases. Consequently, the SME-1 structure cannot accommodate the essential catalytic water molecule found between Ser70 and Glu166 in the other class A beta-lactamases described so far, suggesting that a significant conformational change may be necessary in SME-1 to properly position the hydrolytic water molecule involved in the hydrolysis of the acyl-enzyme intermediate.
About this Structure
1DY6 is a Single protein structure of sequence from Serratia marcescens. Active as Beta-lactamase, with EC number 3.5.2.6 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Structure of the imipenem-hydrolyzing class A beta-lactamase SME-1 from Serratia marcescens., Sougakoff W, L'Hermite G, Pernot L, Naas T, Guillet V, Nordmann P, Jarlier V, Delettre J, Acta Crystallogr D Biol Crystallogr. 2002 Feb;58(Pt 2):267-74. Epub 2002, Jan 24. PMID:11807251
Page seeded by OCA on Thu Feb 21 12:21:48 2008
