4k2f

From Proteopedia

(Difference between revisions)

Revision as of 18:55, 24 December 2014

Structure of Pseudomonas aeruginosa PvdQ bound to BRD-A08522488

Structural highlights

4k2f is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3sra, 3srb, 3src, 4k2g
Activity:	Acyl-homoserine-lactone acylase, with EC number 3.5.1.97
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PVDQ_PSEAE] Catalyzes the deacylation of acyl-homoserine lactone (AHL or acyl-HSL), releasing homoserine lactone (HSL) and the corresponding fatty acid. Possesses a specificity for the degradation of long-chain acyl-HSLs (side chains of 11 to 14 carbons in length). Degrades 3-oxo-C12-HSL, one of the two main AHL signal molecules of P.aeruginosa, and thereby functions as a quorum quencher, inhibiting the las quorum-sensing system. Therefore, may enable P.aeruginosa to modulate its own quorum-sensing-dependent pathogenic potential. Also appears to be required for pyoverdin biosynthesis.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Pseudomonas aeruginosa produces the peptide siderophore pyoverdine, which is used to acquire essential Fe3+ ions from the environment. PvdQ, an Ntn hydrolase, is required for the biosynthesis of pyoverdine. PvdQ knockout strains are not infectious in model systems, suggesting that disruption of siderophore production via PvdQ inhibition could be exploited as a target for novel antibacterial agents, by preventing cells from acquiring iron in the low iron environments of most biological settings. We have previously described a high-throughput screen to identify inhibitors of PvdQ that identified inhibitors with IC50 values of approximately 100 muM. Here, we describe the discovery of ML318, a biaryl nitrile inhibitor of PvdQ acylase. ML318 inhibits PvdQ in vitro (IC50 = 20 nM) by binding in the acyl-binding site, as confirmed by the X-ray crystal structure of PvdQ bound to ML318. Additionally, the PvdQ inhibitor is active in a whole cell assay, preventing pyoverdine production and limiting the growth of P. aeruginosa under iron-limiting conditions.

Identification of Inhibitors of PvdQ, an Enzyme Involved in the Synthesis of the Siderophore Pyoverdine.,Wurst JM, Drake EJ, Theriault JR, Jewett IT, VerPlank L, Perez JR, Dandapani S, Palmer M, Moskowitz SM, Schreiber SL, Munoz B, Gulick AM ACS Chem Biol. 2014 May 21. PMID:24824984^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sio CF, Otten LG, Cool RH, Diggle SP, Braun PG, Bos R, Daykin M, Camara M, Williams P, Quax WJ. Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1. Infect Immun. 2006 Mar;74(3):1673-82. PMID:16495538 doi:74/3/1673
↑ Huang JJ, Han JI, Zhang LH, Leadbetter JR. Utilization of acyl-homoserine lactone quorum signals for growth by a soil pseudomonad and Pseudomonas aeruginosa PAO1. Appl Environ Microbiol. 2003 Oct;69(10):5941-9. PMID:14532048
↑ Lamont IL, Martin LW. Identification and characterization of novel pyoverdine synthesis genes in Pseudomonas aeruginosa. Microbiology. 2003 Apr;149(Pt 4):833-42. PMID:12686626
↑ Wurst JM, Drake EJ, Theriault JR, Jewett IT, VerPlank L, Perez JR, Dandapani S, Palmer M, Moskowitz SM, Schreiber SL, Munoz B, Gulick AM. Identification of Inhibitors of PvdQ, an Enzyme Involved in the Synthesis of the Siderophore Pyoverdine. ACS Chem Biol. 2014 May 21. PMID:24824984 doi:http://dx.doi.org/10.1021/cb5001586

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4k2f"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4k2f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K2F FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A08:(2S)-(4-CHLOROPHENYL)(6-CHLOROPYRIDIN-2-YL)ETHANENITRILE'>A08</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A08:(2S)-(4-CHLOROPHENYL)(6-CHLOROPYRIDIN-2-YL)ETHANENITRILE'>A08</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sra|3sra]], [[3srb|3srb]], [[3src|3src]], [[4k2g|4k2g]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sra|3sra]], [[3srb|3srb]], [[3src|3src]], [[4k2g|4k2g]]</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acyl-homoserine-lactone_acylase Acyl-homoserine-lactone acylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.97 3.5.1.97] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acyl-homoserine-lactone_acylase Acyl-homoserine-lactone acylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.97 3.5.1.97] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k2f RCSB], [http://www.ebi.ac.uk/pdbsum/4k2f PDBsum]</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=4k2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k2f RCSB], [http://www.ebi.ac.uk/pdbsum/4k2f PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PVDQ_PSEAE PVDQ_PSEAE]] Catalyzes the deacylation of acyl-homoserine lactone (AHL or acyl-HSL), releasing homoserine lactone (HSL) and the corresponding fatty acid. Possesses a specificity for the degradation of long-chain acyl-HSLs (side chains of 11 to 14 carbons in length). Degrades 3-oxo-C12-HSL, one of the two main AHL signal molecules of P.aeruginosa, and thereby functions as a quorum quencher, inhibiting the las quorum-sensing system. Therefore, may enable P.aeruginosa to modulate its own quorum-sensing-dependent pathogenic potential. Also appears to be required for pyoverdin biosynthesis.<ref>PMID:16495538</ref> <ref>PMID:14532048</ref> <ref>PMID:12686626</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 </StructureSection>
 [[Category: Acyl-homoserine-lactone acylase]]
-[[Category: Drake, E J.]]
+[[Category: Drake, E J]]
-[[Category: Gulick, A M.]]
+[[Category: Gulick, A M]]
-[[Category: Munoz, B.]]
+[[Category: Munoz, B]]
-[[Category: Theriault, J R.]]
+[[Category: Theriault, J R]]
-[[Category: Wurst, J M.]]
+[[Category: Wurst, J M]]
 [[Category: Amidohydrolase]]
 [[Category: Bacterial protein]]

4k2f

From Proteopedia

Revision as of 18:55, 24 December 2014

Structure of Pseudomonas aeruginosa PvdQ bound to BRD-A08522488

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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