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==Crystal structure of Medicago truncatula histidinol-phosphate aminotransferase (HISN6) in complex with histidinol-phosphate== | |||
<StructureSection load='8bj3' size='340' side='right'caption='[[8bj3]], [[Resolution|resolution]] 1.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8bj3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Medicago_truncatula Medicago truncatula]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BJ3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QNX:[(2~{S})-3-(1~{H}-imidazol-4-yl)-2-[[2-methyl-3-oxidanyl-5-(phosphonooxymethyl)pyridin-4-yl]methylamino]propyl]+dihydrogen+phosphate'>QNX</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=8bj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bj3 OCA], [https://pdbe.org/8bj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bj3 RCSB], [https://www.ebi.ac.uk/pdbsum/8bj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bj3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A072U7F9_MEDTR A0A072U7F9_MEDTR] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Histidinol-phosphate aminotransferase is the sixth protein (hence HISN6) in the histidine biosynthetic pathway in plants. HISN6 is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the reversible conversion of imidazole acetol phosphate into L-histidinol phosphate (HOLP). Here, we show that plant HISN6 enzymes are closely related to the orthologs from Chloroflexota. The studied example, HISN6 from Medicago truncatula (MtHISN6), exhibits a surprisingly high affinity for HOLP, which is much higher than reported for bacterial homologs. Moreover, unlike the latter, MtHISN6 does not transaminate phenylalanine. High-resolution crystal structures of MtHISN6 in the open and closed states, as well as the complex with HOLP and the apo structure without PLP, bring new insights into the enzyme dynamics, pointing at a particular role of a string-like fragment that oscillates near the active site and participates in the HOLP binding. When MtHISN6 is compared to bacterial orthologs with known structures, significant differences arise in or near the string region. The high affinity of MtHISN6 appears linked to the particularly tight active site cavity. Finally, a virtual screening against a library of over 1.3 mln compounds revealed three sites in the MtHISN6 structure with the potential to bind small molecules. Such compounds could be developed into herbicides inhibiting plant HISN6 enzymes absent in animals, which makes them a potential target for weed control agents. | |||
Insights into the substrate specificity, structure, and dynamics of plant histidinol-phosphate aminotransferase (HISN6).,Rutkiewicz M, Nogues I, Witek W, Angelaccio S, Contestabile R, Ruszkowski M Plant Physiol Biochem. 2023 Feb 10;196:759-773. doi: , 10.1016/j.plaphy.2023.02.017. PMID:36842242<ref>PMID:36842242</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8bj3" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Medicago truncatula]] | |||
[[Category: Ruszkowski M]] | |||
[[Category: Rutkiewicz M]] | |||
Revision as of 10:22, 22 March 2023
Crystal structure of Medicago truncatula histidinol-phosphate aminotransferase (HISN6) in complex with histidinol-phosphateCrystal structure of Medicago truncatula histidinol-phosphate aminotransferase (HISN6) in complex with histidinol-phosphate
Structural highlights
FunctionPublication Abstract from PubMedHistidinol-phosphate aminotransferase is the sixth protein (hence HISN6) in the histidine biosynthetic pathway in plants. HISN6 is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the reversible conversion of imidazole acetol phosphate into L-histidinol phosphate (HOLP). Here, we show that plant HISN6 enzymes are closely related to the orthologs from Chloroflexota. The studied example, HISN6 from Medicago truncatula (MtHISN6), exhibits a surprisingly high affinity for HOLP, which is much higher than reported for bacterial homologs. Moreover, unlike the latter, MtHISN6 does not transaminate phenylalanine. High-resolution crystal structures of MtHISN6 in the open and closed states, as well as the complex with HOLP and the apo structure without PLP, bring new insights into the enzyme dynamics, pointing at a particular role of a string-like fragment that oscillates near the active site and participates in the HOLP binding. When MtHISN6 is compared to bacterial orthologs with known structures, significant differences arise in or near the string region. The high affinity of MtHISN6 appears linked to the particularly tight active site cavity. Finally, a virtual screening against a library of over 1.3 mln compounds revealed three sites in the MtHISN6 structure with the potential to bind small molecules. Such compounds could be developed into herbicides inhibiting plant HISN6 enzymes absent in animals, which makes them a potential target for weed control agents. Insights into the substrate specificity, structure, and dynamics of plant histidinol-phosphate aminotransferase (HISN6).,Rutkiewicz M, Nogues I, Witek W, Angelaccio S, Contestabile R, Ruszkowski M Plant Physiol Biochem. 2023 Feb 10;196:759-773. doi: , 10.1016/j.plaphy.2023.02.017. PMID:36842242[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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