1jw0: Difference between revisions

Revision as of 14:27, 21 February 2008

Structure of cephalosporin acylase in complex with glutarate

OverviewOverview

BACKGROUND: Semisynthetic cephalosporins are primarily synthesized from 7-aminocephalosporanic acid (7-ACA), which is obtained by environmentally toxic chemical deacylation of cephalosporin C (CPC). Thus, the enzymatic conversion of CPC to 7-ACA by cephalosporin acylase (CA) would be of great interest. However, CAs use glutaryl-7-ACA (GL-7-ACA) as a primary substrate and the enzyme has low turnover rates for CPC. RESULTS: The binary complex structures of CA with GL-7-ACA and glutarate (the side-chain of GL-7-ACA) show extensive interactions between the glutaryl moiety of GL-7-ACA and the seven residues that form the side-chain pocket. These interactions explain why the D-alpha-aminoadipyl side-chain of CPC yields a poorer substrate than GL-7-ACA. CONCLUSIONS: This understanding of the nature of substrate specificity may be useful in the design of an enzyme with an improved performance for the conversion of CPC to 7-ACA. Additionally, the catalytic mechanism of the deacylation reaction was revealed by the ligand bound structures.

About this StructureAbout this Structure

1JW0 is a Protein complex structure of sequences from Brevundimonas diminuta with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Structure of cephalosporin acylase in complex with glutaryl-7-aminocephalosporanic acid and glutarate: insight into the basis of its substrate specificity., Kim Y, Hol WG, Chem Biol. 2001 Dec;8(12):1253-64. PMID:11755403

Page seeded by OCA on Thu Feb 21 13:27:22 2008

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OCA

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-[[Image:1jw0.gif|left|200px]]<br /><applet load="1jw0" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1jw0.gif|left|200px]]<br /><applet load="1jw0" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1jw0, resolution 2.5&Aring;" />
 '''Structure of cephalosporin acylase in complex with glutarate'''<br />
 ==Overview==
-BACKGROUND: Semisynthetic cephalosporins are primarily synthesized from, 7-aminocephalosporanic acid (7-ACA), which is obtained by environmentally, toxic chemical deacylation of cephalosporin C (CPC). Thus, the enzymatic, conversion of CPC to 7-ACA by cephalosporin acylase (CA) would be of great, interest. However, CAs use glutaryl-7-ACA (GL-7-ACA) as a primary, substrate and the enzyme has low turnover rates for CPC. RESULTS: The, binary complex structures of CA with GL-7-ACA and glutarate (the, side-chain of GL-7-ACA) show extensive interactions between the glutaryl, moiety of GL-7-ACA and the seven residues that form the side-chain pocket., These interactions explain why the D-alpha-aminoadipyl side-chain of CPC, yields a poorer substrate than GL-7-ACA. CONCLUSIONS: This understanding, of the nature of substrate specificity may be useful in the design of an, enzyme with an improved performance for the conversion of CPC to 7-ACA., Additionally, the catalytic mechanism of the deacylation reaction was, revealed by the ligand bound structures.
+BACKGROUND: Semisynthetic cephalosporins are primarily synthesized from 7-aminocephalosporanic acid (7-ACA), which is obtained by environmentally toxic chemical deacylation of cephalosporin C (CPC). Thus, the enzymatic conversion of CPC to 7-ACA by cephalosporin acylase (CA) would be of great interest. However, CAs use glutaryl-7-ACA (GL-7-ACA) as a primary substrate and the enzyme has low turnover rates for CPC. RESULTS: The binary complex structures of CA with GL-7-ACA and glutarate (the side-chain of GL-7-ACA) show extensive interactions between the glutaryl moiety of GL-7-ACA and the seven residues that form the side-chain pocket. These interactions explain why the D-alpha-aminoadipyl side-chain of CPC yields a poorer substrate than GL-7-ACA. CONCLUSIONS: This understanding of the nature of substrate specificity may be useful in the design of an enzyme with an improved performance for the conversion of CPC to 7-ACA. Additionally, the catalytic mechanism of the deacylation reaction was revealed by the ligand bound structures.
 ==About this Structure==
-JW0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Brevundimonas_diminuta Brevundimonas diminuta] with GUA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JW0 OCA].
+JW0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Brevundimonas_diminuta Brevundimonas diminuta] with <scene name='pdbligand=GUA:'>GUA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JW0 OCA].
 ==Reference==
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 [[Category: Brevundimonas diminuta]]
 [[Category: Protein complex]]
-[[Category: Hol, W.G.J.]]
+[[Category: Hol, W G.J.]]
 [[Category: Kim, Y.]]
 [[Category: GUA]]
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 [[Category: glutaryll-7-aca]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:37:30 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:27:22 2008''