4f7v
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4f7v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F7V FirstGlance]. <br> | <table><tr><td colspan='2'>[[4f7v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F7V FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J1D:5-{[2-({N-[(2-AMINO-7,7-DIMETHYL-4-OXO-3,4,7,8-TETRAHYDROPTERIDIN-6-YL)CARBONYL]GLYCYL}AMINO)ETHYL]SULFONYL}-5-DEOXYADENOSINE'>J1D</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J1D:5-{[2-({N-[(2-AMINO-7,7-DIMETHYL-4-OXO-3,4,7,8-TETRAHYDROPTERIDIN-6-YL)CARBONYL]GLYCYL}AMINO)ETHYL]SULFONYL}-5-DEOXYADENOSINE'>J1D</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=4f7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7v OCA], [https://pdbe.org/4f7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f7v RCSB], [https://www.ebi.ac.uk/pdbsum/4f7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7v ProSAT]</span></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=4f7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7v OCA], [https://pdbe.org/4f7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f7v RCSB], [https://www.ebi.ac.uk/pdbsum/4f7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/HPPK_ECOLI HPPK_ECOLI] | [https://www.uniprot.org/uniprot/HPPK_ECOLI HPPK_ECOLI] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthesis pathway catalyzing the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin, is an attractive target for developing novel antimicrobial agents. Previously, we studied the mechanism of HPPK action, synthesized bisubstrate analog inhibitors by linking 6-hydroxymethylpterin to adenosine through phosphate groups, and developed a new generation of bisubstrate inhibitors by replacing the phosphate bridge with a piperidine-containing linkage. To further improve linker properties, we have synthesized a new compound, characterized its protein binding/inhibiting properties, and determined its structure in complex with HPPK. Surprisingly, this inhibitor exhibits a new binding mode in that the adenine base is flipped when compared to previously reported structures. Furthermore, the side chain of amino acid residue E77 is involved in protein-inhibitor interaction, forming hydrogen bonds with both 2' and 3' hydroxyl groups of the ribose moiety. Residue E77 is conserved among HPPK sequences, but interacts only indirectly with the bound MgATP via water molecules. Never observed before, the E77-ribose interaction is compatible only with the new inhibitor-binding mode. Therefore, this compound represents a new direction for further development. | ||
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| - | Bisubstrate analog inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New lead exhibits a distinct binding mode.,Shi G, Shaw G, Li Y, Wu Y, Yan H, Ji X Bioorg Med Chem. 2012 Jul 15;20(14):4303-9. Epub 2012 Jun 6. PMID:22727779<ref>PMID:22727779</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4f7v" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[HPPK 3D structures|HPPK 3D structures]] | *[[HPPK 3D structures|HPPK 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of E. coli HPPK in complex with bisubstrate analogue inhibitor J1D (HP26)
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