1e4d: Difference between revisions

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STRUCTURE OF OXA10 BETA-LACTAMASE AT PH 8.3

OverviewOverview

BACKGROUND: beta-lactam antibiotic therapies are commonly challenged by the hydrolytic activities of beta-lactamases in bacteria. These enzymes have been grouped into four classes: A, B, C, and D. Class B beta-lactamases are zinc dependent, and enzymes of classes A, C, and D are transiently acylated on a serine residue in the course of the turnover chemistry. While class A and C beta-lactamases have been extensively characterized by biochemical and structural methods, class D enzymes remain the least studied despite their increasing importance in the clinic. RESULTS: The crystal structure of the OXA10 class D beta-lactamase has been solved to 1.66 A resolution from a gold derivative and MAD phasing. This structure reveals that beta-lactamases from classes D and A, despite very poor sequence similarity, share a similar overall fold. An additional beta strand in OXA10 mediates the association into dimers characterized by analytical ultracentrifugation. Major differences are found when comparing the molecular details of the active site of this class D enzyme to the corresponding regions in class A and C beta-lactamases. In the native structure of the OXA10 enzyme solved to 1.8 A, Lys-70 is carbamylated. CONCLUSIONS: Several features were revealed by this study: the dimeric structure of the OXA10 beta-lactamase, an extension of the substrate binding site which suggests that class D enzymes may bind other substrates beside beta-lactams, and carbamylation of the active site Lys-70 residue. The CO2-dependent activity of the OXA10 enzyme and the kinetic properties of the natural OXA17 mutant protein suggest possible relationships between carbamylation, inhibition of the enzyme by anions, and biphasic behavior of the enzyme.

About this StructureAbout this Structure

1E4D is a Single protein structure of sequence from Pseudomonas aeruginosa with and as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.

ReferenceReference

Insights into class D beta-lactamases are revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa., Maveyraud L, Golemi D, Kotra LP, Tranier S, Vakulenko S, Mobashery S, Samama JP, Structure. 2000 Dec 15;8(12):1289-98. PMID:11188693

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-[[Image:1e4d.jpg|left|200px]]<br /><applet load="1e4d" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1e4d.jpg|left|200px]]<br /><applet load="1e4d" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1e4d, resolution 1.8&Aring;" />
 '''STRUCTURE OF OXA10 BETA-LACTAMASE AT PH 8.3'''<br />
 ==Overview==
-BACKGROUND: beta-lactam antibiotic therapies are commonly challenged by, the hydrolytic activities of beta-lactamases in bacteria. These enzymes, have been grouped into four classes: A, B, C, and D. Class B, beta-lactamases are zinc dependent, and enzymes of classes A, C, and D are, transiently acylated on a serine residue in the course of the turnover, chemistry. While class A and C beta-lactamases have been extensively, characterized by biochemical and structural methods, class D enzymes, remain the least studied despite their increasing importance in the, clinic. RESULTS: The crystal structure of the OXA10 class D beta-lactamase, has been solved to 1.66 A resolution from a gold derivative and MAD, phasing. This structure reveals that beta-lactamases from classes D and A, despite very poor sequence similarity, share a similar overall fold. An, additional beta strand in OXA10 mediates the association into dimers, characterized by analytical ultracentrifugation. Major differences are, found when comparing the molecular details of the active site of this, class D enzyme to the corresponding regions in class A and C, beta-lactamases. In the native structure of the OXA10 enzyme solved to 1.8, A, Lys-70 is carbamylated. CONCLUSIONS: Several features were revealed by, this study: the dimeric structure of the OXA10 beta-lactamase, an, extension of the substrate binding site which suggests that class D, enzymes may bind other substrates beside beta-lactams, and carbamylation, of the active site Lys-70 residue. The CO2-dependent activity of the OXA10, enzyme and the kinetic properties of the natural OXA17 mutant protein, suggest possible relationships between carbamylation, inhibition of the, enzyme by anions, and biphasic behavior of the enzyme.
+BACKGROUND: beta-lactam antibiotic therapies are commonly challenged by the hydrolytic activities of beta-lactamases in bacteria. These enzymes have been grouped into four classes: A, B, C, and D. Class B beta-lactamases are zinc dependent, and enzymes of classes A, C, and D are transiently acylated on a serine residue in the course of the turnover chemistry. While class A and C beta-lactamases have been extensively characterized by biochemical and structural methods, class D enzymes remain the least studied despite their increasing importance in the clinic. RESULTS: The crystal structure of the OXA10 class D beta-lactamase has been solved to 1.66 A resolution from a gold derivative and MAD phasing. This structure reveals that beta-lactamases from classes D and A, despite very poor sequence similarity, share a similar overall fold. An additional beta strand in OXA10 mediates the association into dimers characterized by analytical ultracentrifugation. Major differences are found when comparing the molecular details of the active site of this class D enzyme to the corresponding regions in class A and C beta-lactamases. In the native structure of the OXA10 enzyme solved to 1.8 A, Lys-70 is carbamylated. CONCLUSIONS: Several features were revealed by this study: the dimeric structure of the OXA10 beta-lactamase, an extension of the substrate binding site which suggests that class D enzymes may bind other substrates beside beta-lactams, and carbamylation of the active site Lys-70 residue. The CO2-dependent activity of the OXA10 enzyme and the kinetic properties of the natural OXA17 mutant protein suggest possible relationships between carbamylation, inhibition of the enzyme by anions, and biphasic behavior of the enzyme.
 ==About this Structure==
-E4D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with SO4 and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1E4D OCA].
+E4D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E4D OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Golemi, D.]]
-[[Category: Kotra, L.P.]]
+[[Category: Kotra, L P.]]
 [[Category: Maveyraud, L.]]
 [[Category: Mobashery, S.]]
-[[Category: Samama, J.P.]]
+[[Category: Samama, J P.]]
 [[Category: Tranier, S.]]
 [[Category: Vakulenko, S.]]
@@ Line 26: / Line 26: @@
 [[Category: beta-lactamase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:46:21 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:23:39 2008''