View source for 7thq


==Crystal structure of PltF trapped with PigG using a proline adenosine vinylsulfonamide inhibitor==
<StructureSection load='7thq' size='340' side='right'caption='[[7thq]], [[Resolution|resolution]] 2.46&Aring;' 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]] 2.46&#8491;</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:(2~{R})-~{N}-[3-[2-[(1~{S})-2-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methylsulfamoyl]-1-[(2~{S})-pyrrolidin-2-yl]ethyl]sulfanylethylamino]-3-oxidanylidene-propyl]-3,3-dimethyl-2-oxidanyl-4-phosphooxy-butanamide'>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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</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]]