2b4k: Difference between revisions

Revision as of 17:34, 21 February 2008

Acetobacter turbidans alpha-amino acid ester hydrolase complexed with phenylglycine

OverviewOverview

The alpha-amino acid ester hydrolase (AEH) from Acetobacter turbidans is a bacterial enzyme catalyzing the hydrolysis and synthesis of beta-lactam antibiotics. The crystal structures of the native enzyme, both unliganded and in complex with the hydrolysis product D-phenylglycine are reported, as well as the structures of an inactive mutant (S205A) complexed with the substrate ampicillin, and an active site mutant (Y206A) with an increased tendency to catalyze antibiotic production rather than hydrolysis. The structure of the native enzyme shows an acyl binding pocket, in which D-phenylglycine binds, and an additional space that is large enough to accommodate the beta-lactam moiety of an antibiotic. In the S205A mutant, ampicillin binds in this pocket in a non-productive manner, making extensive contacts with the side chain of Tyr(112), which also participates in oxyanion hole formation. In the Y206A mutant, the Tyr(112) side chain has moved with its hydroxyl group toward the catalytic serine. Because this changes the properties of the beta-lactam binding site, this could explain the increased beta-lactam transferase activity of this mutant.

About this StructureAbout this Structure

2B4K is a Single protein structure of sequence from Acetobacter pasteurianus with and as ligands. Active as Alpha-amino-acid esterase, with EC number 3.1.1.43 Full crystallographic information is available from OCA.

ReferenceReference

Acetobacter turbidans alpha-amino acid ester hydrolase: how a single mutation improves an antibiotic-producing enzyme., Barends TR, Polderman-Tijmes JJ, Jekel PA, Williams C, Wybenga G, Janssen DB, Dijkstra BW, J Biol Chem. 2006 Mar 3;281(9):5804-10. Epub 2005 Dec 23. PMID:16377627

Page seeded by OCA on Thu Feb 21 16:34:04 2008

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OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-The alpha-amino acid ester hydrolase (AEH) from Acetobacter turbidans is a, bacterial enzyme catalyzing the hydrolysis and synthesis of beta-lactam, antibiotics. The crystal structures of the native enzyme, both unliganded, and in complex with the hydrolysis product D-phenylglycine are reported, as well as the structures of an inactive mutant (S205A) complexed with the, substrate ampicillin, and an active site mutant (Y206A) with an increased, tendency to catalyze antibiotic production rather than hydrolysis. The, structure of the native enzyme shows an acyl binding pocket, in which, D-phenylglycine binds, and an additional space that is large enough to, accommodate the beta-lactam moiety of an antibiotic. In the S205A mutant, ampicillin binds in this pocket in a non-productive manner, making, extensive contacts with the side chain of Tyr(112), which also, participates in oxyanion hole formation. In the Y206A mutant, the Tyr(112), side chain has moved with its hydroxyl group toward the catalytic serine., Because this changes the properties of the beta-lactam binding site, this, could explain the increased beta-lactam transferase activity of this, mutant.
+The alpha-amino acid ester hydrolase (AEH) from Acetobacter turbidans is a bacterial enzyme catalyzing the hydrolysis and synthesis of beta-lactam antibiotics. The crystal structures of the native enzyme, both unliganded and in complex with the hydrolysis product D-phenylglycine are reported, as well as the structures of an inactive mutant (S205A) complexed with the substrate ampicillin, and an active site mutant (Y206A) with an increased tendency to catalyze antibiotic production rather than hydrolysis. The structure of the native enzyme shows an acyl binding pocket, in which D-phenylglycine binds, and an additional space that is large enough to accommodate the beta-lactam moiety of an antibiotic. In the S205A mutant, ampicillin binds in this pocket in a non-productive manner, making extensive contacts with the side chain of Tyr(112), which also participates in oxyanion hole formation. In the Y206A mutant, the Tyr(112) side chain has moved with its hydroxyl group toward the catalytic serine. Because this changes the properties of the beta-lactam binding site, this could explain the increased beta-lactam transferase activity of this mutant.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Alpha-amino-acid esterase]]
 [[Category: Single protein]]
-[[Category: Barends, T.R.M.]]
+[[Category: Barends, T R.M.]]
-[[Category: Dijkstra, B.W.]]
+[[Category: Dijkstra, B W.]]
-[[Category: Janssen, D.B.]]
+[[Category: Janssen, D B.]]
-[[Category: Jekel, P.A.]]
+[[Category: Jekel, P A.]]
-[[Category: Polderman-Tijmes, J.J.]]
+[[Category: Polderman-Tijmes, J J.]]
 [[Category: Williams, C.]]
 [[Category: Wybenga, G.]]
@@ Line 25: / Line 25: @@
 [[Category: alpha-beta hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:30:41 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:34:04 2008''