This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1gk0
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1gk0.gif|left|200px]] | [[Image:1gk0.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1gk0", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1gk0| PDB=1gk0 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''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''' | ||
| Line 34: | Line 31: | ||
[[Category: Sauber, K.]] | [[Category: Sauber, K.]] | ||
[[Category: Schreuder, H.]] | [[Category: Schreuder, H.]] | ||
| - | [[Category: | + | [[Category: Catalytic triad]] |
| - | [[Category: | + | [[Category: Cephalosporin acylase]] |
| - | [[Category: | + | [[Category: Cephalosporin c]] |
| - | [[Category: | + | [[Category: Glutaryl acylase]] |
| - | [[Category: | + | [[Category: Ntn-hydrolase]] |
| - | [[Category: | + | [[Category: X-raz structure]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:40:18 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:40, 2 May 2008
STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C
Overview
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.
About this Structure
1GK0 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 Fri May 2 17:40:18 2008
