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4oon

From Proteopedia

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Revision as of 07:36, 25 January 2023

Crystal structure of PBP1a in complex with compound 17 ((4Z,8S,11E,14S)-5-(2-amino-1,3-thiazol-4-yl)-14-(5,6-dihydroxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-8-formyl-2-methyl-6-oxo-3,10-dioxa-4,7,11-triazatetradeca-4,11-diene-2,12,14-tricarboxylic acid)

Structural highlights

4oon is a 1 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PBPA_PSEAE Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity).

Publication Abstract from PubMed

Multidrug-resistant Gram-negative pathogens are an emerging threat to human health, and addressing this challenge will require development of new antibacterial agents. This can be achieved through an improved molecular understanding of drug-target interactions combined with enhanced delivery of these agents to the site of action. Herein we describe the first application of siderophore receptor-mediated drug uptake of lactivicin analogues as a strategy that enables the development of novel antibacterial agents against clinically relevant Gram-negative bacteria. We report the first crystal structures of several sideromimic conjugated compounds bound to penicillin binding proteins PBP3 and PBP1a from Pseudomonas aeruginosa and characterize the reactivity of lactivicin and beta-lactam core structures. Results from drug sensitivity studies with beta-lactamase enzymes are presented, as well as a structure-based hypothesis to reduce susceptibility to this enzyme class. Finally, mechanistic studies demonstrating that sideromimic modification alters the drug uptake process are discussed.

Siderophore Receptor-Mediated Uptake of Lactivicin Analogues in Gram-Negative Bacteria.,Starr J, Brown MF, Aschenbrenner L, Caspers N, Che Y, Gerstenberger BS, Huband M, Knafels JD, Lemmon MM, Li C, McCurdy SP, McElroy E, Rauckhorst MR, Tomaras AP, Young JA, Zaniewski RP, Shanmugasundaram V, Han S J Med Chem. 2014 Apr 21. PMID:24694215^[1]

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

References

↑ Starr J, Brown MF, Aschenbrenner L, Caspers N, Che Y, Gerstenberger BS, Huband M, Knafels JD, Lemmon MM, Li C, McCurdy SP, McElroy E, Rauckhorst MR, Tomaras AP, Young JA, Zaniewski RP, Shanmugasundaram V, Han S. Siderophore Receptor-Mediated Uptake of Lactivicin Analogues in Gram-Negative Bacteria. J Med Chem. 2014 Apr 21. PMID:24694215 doi:http://dx.doi.org/10.1021/jm500219c

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Large Structures | Pseudomonas aeruginosa PAO1 | Caspers N | Han S | Knafels JD

@@ Line 3: / Line 3: @@
 <StructureSection load='4oon' size='340' side='right'caption='[[4oon]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4oon]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OON OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OON FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4oon]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OON FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2U4:(4Z,8S,11E,14S)-5-(2-AMINO-1,3-THIAZOL-4-YL)-14-(5,6-DIHYDROXY-1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)-8-FORMYL-2-METHYL-6-OXO-3,10-DIOXA-4,7,11-TRIAZATETRADECA-4,11-DIENE-2,12,14-TRICARBOXYLIC+ACID'>2U4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2U4:(4Z,8S,11E,14S)-5-(2-AMINO-1,3-THIAZOL-4-YL)-14-(5,6-DIHYDROXY-1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)-8-FORMYL-2-METHYL-6-OXO-3,10-DIOXA-4,7,11-TRIAZATETRADECA-4,11-DIENE-2,12,14-TRICARBOXYLIC+ACID'>2U4</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ool|4ool]], [[4oom|4oom]]</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=4oon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oon OCA], [https://pdbe.org/4oon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oon RCSB], [https://www.ebi.ac.uk/pdbsum/4oon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oon ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mrcA, ponA, PA5045 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</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=4oon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oon OCA], [http://pdbe.org/4oon PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oon RCSB], [http://www.ebi.ac.uk/pdbsum/4oon PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oon ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PBPA_PSEAE PBPA_PSEAE]] Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity).
+[https://www.uniprot.org/uniprot/PBPA_PSEAE PBPA_PSEAE] Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 18: @@
 </div>
 <div class="pdbe-citations 4oon" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Pseae]]
+[[Category: Pseudomonas aeruginosa PAO1]]
-[[Category: Caspers, N]]
+[[Category: Caspers N]]
-[[Category: Han, S]]
+[[Category: Han S]]
-[[Category: Knafels, J D]]
+[[Category: Knafels JD]]
-[[Category: Pbp1a]]
-[[Category: Transferase-transferase inhibitor complex]]

4oon

From Proteopedia

Revision as of 07:36, 25 January 2023

Crystal structure of PBP1a in complex with compound 17 ((4Z,8S,11E,14S)-5-(2-amino-1,3-thiazol-4-yl)-14-(5,6-dihydroxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-8-formyl-2-methyl-6-oxo-3,10-dioxa-4,7,11-triazatetradeca-4,11-diene-2,12,14-tricarboxylic acid)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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