1gk1
From Proteopedia
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| - | {{STRUCTURE_1gk1| PDB=1gk1 | SCENE= }} | ||
| - | ===STRUCTURE-BASED PREDICTION OF MODIFICATIONS IN GLUTARYLAMIDASE TO ALLOW SINGLE-STEP ENZYMATIC PRODUCTION OF 7-AMINOCEPHALOSPORANIC ACID FROM CEPHALOSPORIN C=== | ||
| - | {{ABSTRACT_PUBMED_11742126}} | ||
| - | == | + | ==Structure-based prediction of modifications in glutarylamidase to allow single-step enzymatic production of 7-aminocephalosporanic acid from cephalosporin C== |
| - | [[1gk1]] is a 4 chain structure with sequence from [ | + | <StructureSection load='1gk1' size='340' side='right'caption='[[1gk1]], [[Resolution|resolution]] 2.40Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1gk1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_sp. Pseudomonas sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GK1 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gk1 OCA], [https://pdbe.org/1gk1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gk1 RCSB], [https://www.ebi.ac.uk/pdbsum/1gk1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gk1 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/G7AC_PSEU7 G7AC_PSEU7] Catalyzes the deacylation of 7 beta-(4-carboxybutanamido)cephalosporanic acid (glutaryl-7-aminocephalosporanic acid or GL-7-ACA) to 7-aminocephalosporanic acid (7-ACA).<ref>PMID:2993240</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/1gk1_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gk1 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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<ref>PMID:11742126</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | < | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 1gk1" style="background-color:#fffaf0;"></div> |
| - | [[Category: Pseudomonas sp | + | |
| - | [[Category: Aretz | + | ==See Also== |
| - | [[Category: Fritz-Wolf | + | *[[Cephalosporin acylase 3D structures|Cephalosporin acylase 3D structures]] |
| - | [[Category: Kabsch | + | == References == |
| - | [[Category: Koller | + | <references/> |
| - | [[Category: Lange | + | __TOC__ |
| - | [[Category: Liesum | + | </StructureSection> |
| - | [[Category: Sauber | + | [[Category: Large Structures]] |
| - | [[Category: Schreuder | + | [[Category: Pseudomonas sp]] |
| - | + | [[Category: Aretz W]] | |
| - | + | [[Category: Fritz-Wolf K]] | |
| - | + | [[Category: Kabsch W]] | |
| - | + | [[Category: Koller KP]] | |
| - | + | [[Category: Lange G]] | |
| - | + | [[Category: Liesum A]] | |
| - | + | [[Category: Sauber K]] | |
| + | [[Category: Schreuder H]] | ||
Current revision
Structure-based prediction of modifications in glutarylamidase to allow single-step enzymatic production of 7-aminocephalosporanic acid from cephalosporin C
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Categories: Large Structures | Pseudomonas sp | Aretz W | Fritz-Wolf K | Kabsch W | Koller KP | Lange G | Liesum A | Sauber K | Schreuder H
