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| | {{STRUCTURE_1gk1| PDB=1gk1 | SCENE= }} | | {{STRUCTURE_1gk1| PDB=1gk1 | SCENE= }} |
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| - | '''STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C'''
| + | ===STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C=== |
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| - | ==Overview==
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| - | Glutarylamidase is an important enzyme employed in the commercial production of 7-aminocephalosporanic acid, a starting compound in the synthesis of cephalosporin antibiotics. 7-aminocephalosporanic acid is obtained from cephalosporin C, a natural antibiotic, either chemically or by a two-step enzymatic process utilizing the enzymes D-amino acid oxidase and glutarylamidase. We have investigated possibilities for redesigning glutarylamidase for the production of 7-aminocephalosporanic acid from cephalosporin C in a single enzymatic step. These studies are based on the structures of glutarylamidase, which we have solved with bound phosphate and ethylene glycol to 2.5 A resolution and with bound glycerol to 2.4 A. The phosphate binds near the catalytic serine in a way that mimics the hemiacetal that develops during catalysis, while the glycerol occupies the side-chain binding pocket. Our structures show that the enzyme is not only structurally similar to penicillin G acylase but also employs essentially the same mechanism in which the alpha-amino group of the catalytic serine acts as a base. A subtle difference is the presence of two catalytic dyads, His B23/Glu B455 and His B23/Ser B1, that are not seen in penicillin G acylase. In contrast to classical serine proteases, the central histidine of these dyads interacts indirectly with the O(gamma) through a hydrogen bond relay network involving the alpha-amino group of the serine and a bound water molecule. A plausible model of the enzyme-substrate complex is proposed that leads to the prediction of mutants of glutarylamidase that should enable the enzyme to deacylate cephalosporin C into 7-aminocephalosporanic acid.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11742126}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11742126 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11742126}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ntn-hydrolase]] | | [[Category: Ntn-hydrolase]] |
| | [[Category: X-raz structure]] | | [[Category: X-raz structure]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:40:22 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 05:24:57 2008'' |
Revision as of 02:24, 1 July 2008
Template:STRUCTURE 1gk1
STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C
Template:ABSTRACT PUBMED 11742126
About this Structure
1GK1 is a Protein complex structure of sequences from Pseudomonas sp.. Full crystallographic information is available from OCA.
Reference
Structure-based prediction of modifications in glutarylamidase to allow single-step enzymatic production of 7-aminocephalosporanic acid from cephalosporin C., Fritz-Wolf K, Koller KP, Lange G, Liesum A, Sauber K, Schreuder H, Aretz W, Kabsch W, Protein Sci. 2002 Jan;11(1):92-103. PMID:11742126
Page seeded by OCA on Tue Jul 1 05:24:57 2008
