1gk0
From Proteopedia
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| - | [[Image:1gk0.gif|left|200px]]<br /><applet load="1gk0" size=" | + | [[Image:1gk0.gif|left|200px]]<br /><applet load="1gk0" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1gk0, resolution 2.50Å" /> | caption="1gk0, resolution 2.50Å" /> | ||
'''STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C'''<br /> | '''STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1GK0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_sp. Pseudomonas sp.] with PO4 and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Penicillin_amidase Penicillin amidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.11 3.5.1.11] Known structural/functional Site: <scene name='pdbsite=POB:Po4 Binding Site For Chain D'>POB</scene>. Full crystallographic information is available from [http:// | + | 1GK0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_sp. Pseudomonas sp.] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Penicillin_amidase Penicillin amidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.11 3.5.1.11] Known structural/functional Site: <scene name='pdbsite=POB:Po4+Binding+Site+For+Chain+D'>POB</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GK0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: x-raz structure]] | [[Category: x-raz structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:40:34 2008'' |
Revision as of 07:40, 3 February 2008
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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. with and as ligands. Active as Penicillin amidase, with EC number 3.5.1.11 Known structural/functional Site: . 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 Sun Feb 3 09:40:34 2008
Categories: Penicillin amidase | Protein complex | Pseudomonas sp. | Aretz, W. | Fritz-Wolf, K. | Kabsch, W. | Koller, K.P. | Lange, G. | Liesum, A. | Sauber, K. | Schreuder, H. | EDO | PO4 | Catalytic triad | Cephalosporin acylase | Cephalosporin c | Glutaryl acylase | Ntn-hydrolase | X-raz structure
