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7thq
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7thq is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of PltF trapped with PigG using a proline adenosine vinylsulfonamide inhibitor== | |
| + | <StructureSection load='7thq' size='340' side='right'caption='[[7thq]], [[Resolution|resolution]] 2.46Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7thq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_protegens_Pf-5 Pseudomonas protegens Pf-5] and [https://en.wikipedia.org/wiki/Serratia_sp._ATCC_39006 Serratia sp. ATCC 39006]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7THQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7THQ 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]] 2.46Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=I5M:5-deoxy-5-({(2S)-2-({2-[(N-{(2R)-4-[(dioxo-lambda~5~-phosphanyl)oxy]-2-hydroxy-3,3-dimethylbutanoyl}-beta-alanyl)amino]ethyl}sulfanyl)-2-[(2S)-pyrrolidin-2-yl]ethanesulfonyl}amino)adenosine'>I5M</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=7thq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7thq OCA], [https://pdbe.org/7thq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7thq RCSB], [https://www.ebi.ac.uk/pdbsum/7thq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7thq ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PLTF_PSEF5 PLTF_PSEF5] Involved in the biosynthesis of pyoluteorin. Catalyzes the conversion of L-proline to L-prolyl-AMP and the transfer of the L-prolyl group to acyl carrier protein PltL.<ref>PMID:11880032</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Non-ribosomal peptides play a critical role in the clinic as therapeutic agents. To access more chemically diverse therapeutics, non-ribosomal peptide synthetases (NRPSs) have been targeted for engineering through combinatorial biosynthesis; however, this has been met with limited success in part due to the lack of proper protein-protein interactions between non-cognate proteins. Herein, we report our use of chemical biology to enable X-ray crystallography, molecular dynamics (MD) simulations, and biochemical studies to elucidate binding specificities between peptidyl carrier proteins (PCPs) and adenylation (A) domains. Specifically, we determined X-ray crystal structures of a type II PCP crosslinked to its cognate A domain, PigG and PigI, and of PigG crosslinked to a non-cognate PigI homologue, PltF. The crosslinked PCP-A domain structures possess large protein-protein interfaces that predominantly feature hydrophobic interactions, with specific electrostatic interactions that orient the substrate for active site delivery. MD simulations of the PCP-A domain complexes and unbound PCP structures provide a dynamical evaluation of the transient interactions formed at PCP-A domain interfaces, which confirm the previously hypothesized role of a PCP loop as a crucial recognition element. Finally, we demonstrate that the interfacial interactions at the PCP loop 1 region can be modified to control PCP binding specificity through gain-of-function mutations. This work suggests that loop conformational preferences and dynamism account for improved shape complementary in the PCP-A domain interactions. Ultimately, these studies show how crystallographic, biochemical, and computational methods can be used to rationally re-engineer NRPSs for non-cognate interactions. | ||
| - | + | Essential Role of Loop Dynamics in Type II NRPS Biomolecular Recognition.,Corpuz JC, Patel A, Davis TD, Podust LM, McCammon JA, Burkart MD ACS Chem Biol. 2022 Oct 21;17(10):2890-2898. doi: 10.1021/acschembio.2c00523. , Epub 2022 Sep 29. PMID:36173802<ref>PMID:36173802</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7thq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pseudomonas protegens Pf-5]] | ||
| + | [[Category: Serratia sp. ATCC 39006]] | ||
| + | [[Category: Corpuz JC]] | ||
| + | [[Category: Podust LM]] | ||
Current revision
Crystal structure of PltF trapped with PigG using a proline adenosine vinylsulfonamide inhibitor
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