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==Crystal Structures of Glutaryl 7-Aminocephalosporanic Acid Acylase: Insight into Autoproteolytic Activation== | |||
<StructureSection load='3s8r' size='340' side='right' caption='[[3s8r]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3s8r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseudomonas Pseudomonas]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1oqz 1oqz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S8R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S8R FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1or0|1or0]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutaryl-7-aminocephalosporanic-acid_acylase Glutaryl-7-aminocephalosporanic-acid acylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.93 3.5.1.93] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s8r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s8r RCSB], [http://www.ebi.ac.uk/pdbsum/3s8r PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Glutaryl 7-aminocephalosporanic acid acylase (GCA, EC 3.5.1.11) is a member of N-terminal nucleophile (Ntn) hydrolases. The native enzyme is an (alpha beta)(2) heterotetramer originated from an enzymatically inactive precursor of a single polypeptide. The activation of precursor GCA consists of primary and secondary autoproteolytic cleavages, generating a terminal residue with both a nucleophile and a base and releasing a nine amino acid spacer peptide. We have determined the crystal structures of the recombinant selenomethionyl native and S170A mutant precursor from Pseudomonas sp. strain GK16. Precursor activation is likely triggered by conformational constraints within the spacer peptide, probably inducing a peptide flip. Autoproteolytic site solvent molecules, which have been trapped in a hydrophobic environment by the spacer peptide, may play a role as a general base for nucleophilic attack. The activation results in building up a catalytic triad composed of Ser170/His192/Glu624. However, the triad is not linked to the usual hydroxyl but the free alpha-amino group of the N-terminal serine residue of the native GCA. Mutagenesis and structural data support the notion that the stabilization of a transient hydroxazolidine ring during autoproteolysis would be critical during the N --> O acyl shift. The autoproteolytic activation mechanism for GCA is described. | |||
Crystal structures of glutaryl 7-aminocephalosporanic acid acylase: insight into autoproteolytic activation.,Kim JK, Yang IS, Rhee S, Dauter Z, Lee YS, Park SS, Kim KH Biochemistry. 2003 Apr 15;42(14):4084-93. PMID:12680762<ref>PMID:12680762</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Glutaryl-7-aminocephalosporanic-acid acylase]] | [[Category: Glutaryl-7-aminocephalosporanic-acid acylase]] | ||
[[Category: Pseudomonas]] | [[Category: Pseudomonas]] | ||
[[Category: Kim, J K | [[Category: Kim, J K]] | ||
[[Category: Kim, K H | [[Category: Kim, K H]] | ||
[[Category: Park, S S | [[Category: Park, S S]] | ||
[[Category: Yang, I S | [[Category: Yang, I S]] | ||
[[Category: Acylase]] | [[Category: Acylase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Motif]] | [[Category: Motif]] | ||
Revision as of 09:57, 21 December 2014
Crystal Structures of Glutaryl 7-Aminocephalosporanic Acid Acylase: Insight into Autoproteolytic ActivationCrystal Structures of Glutaryl 7-Aminocephalosporanic Acid Acylase: Insight into Autoproteolytic Activation
Structural highlights
Publication Abstract from PubMedGlutaryl 7-aminocephalosporanic acid acylase (GCA, EC 3.5.1.11) is a member of N-terminal nucleophile (Ntn) hydrolases. The native enzyme is an (alpha beta)(2) heterotetramer originated from an enzymatically inactive precursor of a single polypeptide. The activation of precursor GCA consists of primary and secondary autoproteolytic cleavages, generating a terminal residue with both a nucleophile and a base and releasing a nine amino acid spacer peptide. We have determined the crystal structures of the recombinant selenomethionyl native and S170A mutant precursor from Pseudomonas sp. strain GK16. Precursor activation is likely triggered by conformational constraints within the spacer peptide, probably inducing a peptide flip. Autoproteolytic site solvent molecules, which have been trapped in a hydrophobic environment by the spacer peptide, may play a role as a general base for nucleophilic attack. The activation results in building up a catalytic triad composed of Ser170/His192/Glu624. However, the triad is not linked to the usual hydroxyl but the free alpha-amino group of the N-terminal serine residue of the native GCA. Mutagenesis and structural data support the notion that the stabilization of a transient hydroxazolidine ring during autoproteolysis would be critical during the N --> O acyl shift. The autoproteolytic activation mechanism for GCA is described. Crystal structures of glutaryl 7-aminocephalosporanic acid acylase: insight into autoproteolytic activation.,Kim JK, Yang IS, Rhee S, Dauter Z, Lee YS, Park SS, Kim KH Biochemistry. 2003 Apr 15;42(14):4084-93. PMID:12680762[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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