View source for 4wl2


==Structure of penicillin V acylase from Pectobacterium atrosepticum==
<StructureSection load='4wl2' size='340' side='right'caption='[[4wl2]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wl2]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Pectobacterium_atrosepticum_SCRI1043 Pectobacterium atrosepticum SCRI1043]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WL2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WL2 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]] 2.5&#8491;</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=4wl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wl2 OCA], [https://pdbe.org/4wl2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wl2 RCSB], [https://www.ebi.ac.uk/pdbsum/4wl2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wl2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PAC_PECAS PAC_PECAS] Catalyzes the hydrolysis of penicillin V to 6-aminopenicillanate (6-APA) (PubMed:23850621, PubMed:25931393, PubMed:26707624). Shows high specificity towards penicillin V (PubMed:23850621). Can use other beta-lactam substrates, including penicillin G, ampicillin, cephalexin, cloxacillin and dicloxacillin, but at a rate less than 10% of that of penicillin V (PubMed:23850621). Does not show any activity with glyco- or tauro-conjugated bile salts (PubMed:23850621).<ref>PMID:23850621</ref> <ref>PMID:25931393</ref> <ref>PMID:26707624</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Penicillin V acylases (PVA) catalyze the deacylation of the beta-lactam antibiotic phenoxymethylpenicillin (Pen V). They are members of the Ntn hydrolase family and possess an N-terminal cysteine as the main catalytic nucleophile residue. They form the evolutionarily related cholylglycine hydrolase (CGH) group which includes bile salt hydrolases (BSH) responsible for bile deconjugation. Even though a few PVA and BSH structures have been reported, no structure of a functional PVA from Gram-negative bacteria is available. Here, we report the crystal structure of a highly active PVA from Gram-negative Pectobacterium atrosepticum (PaPVA) at 2.5A resolution. Structural comparison with PVAs from Gram-positive bacteria revealed that PaPVA had a distinctive tetrameric structure and active site organization. In addition, mutagenesis of key active site residues and biochemical characterization of the resultant variants elucidated the role of these residues in substrate binding and catalysis. The importance of residue Trp23 and Trp87 side chains in binding and correct positioning of Pen V by PVAs was confirmed using mutagenesis and substrate docking with a 15ns molecular dynamics simulation. These results establish the unique nature of Gram-negative CGHs and necessitate further research about their substrate spectrum.

Structural analysis of a penicillin V acylase from Pectobacterium atrosepticum confirms the importance of two Trp residues for activity and specificity.,Avinash VS, Panigrahi P, Chand D, Pundle A, Suresh CG, Ramasamy S J Struct Biol. 2016 Feb;193(2):85-94. doi: 10.1016/j.jsb.2015.12.008. Epub 2015, Dec 18. PMID:26707624<ref>PMID:26707624</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wl2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pectobacterium atrosepticum SCRI1043]]
[[Category: Avinash VS]]
[[Category: Pundle AV]]
[[Category: Ramasamy S]]
[[Category: Suresh CG]]