4s1i: Difference between revisions
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<StructureSection load='4s1i' size='340' side='right'caption='[[4s1i]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='4s1i' size='340' side='right'caption='[[4s1i]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4s1i]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4s1i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enthi Enthi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S1I FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHI_126090 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHI_126090 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5759 ENTHI])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyridoxal_kinase Pyridoxal kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.35 2.7.1.35] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4s1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s1i OCA], [https://pdbe.org/4s1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s1i RCSB], [https://www.ebi.ac.uk/pdbsum/4s1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s1i ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B6 and a cofactor for more than 140 enzymes. This coenzyme plays a pivotal role in catalysis of various enzymatic reactions that are critical for the survival of organisms. Entamoeba histolytica depends on the uptake of pyridoxal (PL), a B6 vitamer from the external environment which is then phosphorylated by pyridoxal kinase (EhPLK) to form PLP via the salvage pathway. E. histolytica cannot synthesise vitamin B6de-novo, and also lacks pyridoxine 5'-phosphate oxidase, a salvage pathway enzyme required to produce PLP from pyridoxine phosphate (PNP) and pyridoxamine phosphate (PMP). Analysing the importance of PLK in E. histolytica, we have determined the high-resolution crystal structures of the dimeric pyridoxal kinase in apo, ADP-bound, and PLP-bound states. These structures provided a snapshot of the transition state and help in understanding the reaction mechanism in greater detail. The EhPLK structure significantly differed from the human homologue at its PLP binding site, and the phylogenetic study also revealed its divergence from human PLK. Further, gene regulation of EhPLK using sense and antisense RNA showed that any change in optimal level is harmful to the pathogen. Biochemical and in vivo studies unveiled EhPLK to be essential for this pathogen, while the molecular differences with human PLK structure can be exploited for the structure-guided design of EhPLK inhibitors. | |||
Characterization and functional insights into the Entamoeba histolytica pyridoxal kinase, an enzyme essential for its survival.,Tarique KF, Devi S, Tomar P, Ali MF, Rehman SAA, Gourinath S J Struct Biol. 2020 Dec 1;212(3):107645. doi: 10.1016/j.jsb.2020.107645. Epub, 2020 Oct 9. PMID:33045383<ref>PMID:33045383</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4s1i" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Pyridoxal kinase|Pyridoxal kinase]] | *[[Pyridoxal kinase|Pyridoxal kinase]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 09:44, 24 March 2021
Pyridoxal Kinase of Entamoeba histolytica with PLPPyridoxal Kinase of Entamoeba histolytica with PLP
Structural highlights
Publication Abstract from PubMedPyridoxal 5'-phosphate (PLP) is the active form of vitamin B6 and a cofactor for more than 140 enzymes. This coenzyme plays a pivotal role in catalysis of various enzymatic reactions that are critical for the survival of organisms. Entamoeba histolytica depends on the uptake of pyridoxal (PL), a B6 vitamer from the external environment which is then phosphorylated by pyridoxal kinase (EhPLK) to form PLP via the salvage pathway. E. histolytica cannot synthesise vitamin B6de-novo, and also lacks pyridoxine 5'-phosphate oxidase, a salvage pathway enzyme required to produce PLP from pyridoxine phosphate (PNP) and pyridoxamine phosphate (PMP). Analysing the importance of PLK in E. histolytica, we have determined the high-resolution crystal structures of the dimeric pyridoxal kinase in apo, ADP-bound, and PLP-bound states. These structures provided a snapshot of the transition state and help in understanding the reaction mechanism in greater detail. The EhPLK structure significantly differed from the human homologue at its PLP binding site, and the phylogenetic study also revealed its divergence from human PLK. Further, gene regulation of EhPLK using sense and antisense RNA showed that any change in optimal level is harmful to the pathogen. Biochemical and in vivo studies unveiled EhPLK to be essential for this pathogen, while the molecular differences with human PLK structure can be exploited for the structure-guided design of EhPLK inhibitors. Characterization and functional insights into the Entamoeba histolytica pyridoxal kinase, an enzyme essential for its survival.,Tarique KF, Devi S, Tomar P, Ali MF, Rehman SAA, Gourinath S J Struct Biol. 2020 Dec 1;212(3):107645. doi: 10.1016/j.jsb.2020.107645. Epub, 2020 Oct 9. PMID:33045383[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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