1jvz: Difference between revisions
New page: left|200px<br /><applet load="1jvz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jvz, resolution 2.6Å" /> '''Structure of cephalos... |
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[[Image:1jvz.gif|left|200px]]<br /><applet load="1jvz" size=" | [[Image:1jvz.gif|left|200px]]<br /><applet load="1jvz" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1jvz, resolution 2.6Å" /> | caption="1jvz, resolution 2.6Å" /> | ||
'''Structure of cephalosporin acylase in complex with glutaryl-7-aminocephalosporanic acid'''<br /> | '''Structure of cephalosporin acylase in complex with glutaryl-7-aminocephalosporanic acid'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Semisynthetic cephalosporins are primarily synthesized from | 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== | ==About this Structure== | ||
1JVZ 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 CEN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1JVZ 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=CEN:'>CEN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JVZ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Brevundimonas diminuta]] | [[Category: Brevundimonas diminuta]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Hol, W | [[Category: Hol, W G.J.]] | ||
[[Category: Kim, Y.]] | [[Category: Kim, Y.]] | ||
[[Category: CEN]] | [[Category: CEN]] | ||
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[[Category: glutaryl-7-aminocephalosporanic acid]] | [[Category: glutaryl-7-aminocephalosporanic acid]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:27:25 2008'' | ||
Revision as of 11:27, 21 February 2008
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Structure of cephalosporin acylase in complex with glutaryl-7-aminocephalosporanic acid
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.
About this Structure
1JVZ is a Protein complex structure of sequences from Brevundimonas diminuta with CEN as ligand. Full crystallographic information is available from OCA.
Reference
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
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