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| | ==Crystal structure of homoserine dehydrogenase in complex with L-cysteine and NAD== | | ==Crystal structure of homoserine dehydrogenase in complex with L-cysteine and NAD== |
| - | <StructureSection load='5x9d' size='340' side='right' caption='[[5x9d]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='5x9d' size='340' side='right'caption='[[5x9d]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x9d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X9D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X9D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x9d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sulfurisphaera_tokodaii_str._7 Sulfurisphaera tokodaii str. 7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X9D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=80F:(2R)-3-[[(4S)-3-aminocarbonyl-1-[(2R,3R,4S,5R)-5-[[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-3,4-bis(oxidanyl)oxolan-2-yl]-4H-pyridin-4-yl]sulfanyl]-2-azanyl-propanoic+acid'>80F</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ydr|4ydr]], [[5avo|5avo]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=80F:(2~{R})-3-[[(4~{S})-3-aminocarbonyl-1-[(2~{R},3~{R},4~{S},5~{R})-5-[[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-3,4-bis(oxidanyl)oxolan-2-yl]-4~{H}-pyridin-4-yl]sulfanyl]-2-azanyl-propanoic+acid'>80F</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Homoserine_dehydrogenase Homoserine dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.3 1.1.1.3] </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=5x9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x9d OCA], [https://pdbe.org/5x9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x9d RCSB], [https://www.ebi.ac.uk/pdbsum/5x9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x9d ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5x9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x9d OCA], [http://pdbe.org/5x9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x9d RCSB], [http://www.ebi.ac.uk/pdbsum/5x9d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x9d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DHOM_SULTO DHOM_SULTO] Catalyzes the conversion of L-aspartate-beta-semialdehyde (L-Asa) to L-homoserine (L-Hse), the third step in the biosynthesis of threonine and methionine from aspartate.<ref>PMID:29124164</ref> <ref>PMID:29636528</ref> <ref>PMID:35835834</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Homoserine dehydrogenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Goto, M]] | + | [[Category: Sulfurisphaera tokodaii str. 7]] |
| - | [[Category: Kaneko, R]] | + | [[Category: Goto M]] |
| - | [[Category: Ogata, K]] | + | [[Category: Kaneko R]] |
| - | [[Category: Yoshimune, K]] | + | [[Category: Ogata K]] |
| - | [[Category: Complex]]
| + | [[Category: Yoshimune K]] |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DHOM_SULTO Catalyzes the conversion of L-aspartate-beta-semialdehyde (L-Asa) to L-homoserine (L-Hse), the third step in the biosynthesis of threonine and methionine from aspartate.[1] [2] [3]
Publication Abstract from PubMed
Homoserine dehydrogenase (EC 1.1.1.3, HSD) is an important regulatory enzyme in the aspartate pathway, which mediates synthesis of methionine, threonine and isoleucine from aspartate. Here, HSD from the hyperthermophilic archaeon Sulfolobus tokodaii (StHSD) was found to be inhibited by cysteine, which acted as a competitive inhibitor of homoserine with a Ki of 11 muM and uncompetitive an inhibitor of NAD and NADP with Ki's of 0.55 and 1.2 mM, respectively. Initial velocity and product (NADH) inhibition analyses of homoserine oxidation indicated that StHSD first binds NAD and then homoserine through a sequentially ordered mechanism. This suggests that feedback inhibition of StHSD by cysteine occurs through the formation of an enzyme-NAD-cysteine complex. Structural analysis of StHSD complexed with cysteine and NAD revealed that cysteine situates within the homoserine binding site. The distance between the sulfur atom of cysteine and the C4 atom of the nicotinamide ring was approximately 1.9 A, close enough to form a covalent bond. The UV absorption-difference spectrum of StHSD with and without cysteine in the presence of NAD, exhibited a peak at 325 nm, which also suggests formation of a covalent bond between cysteine and the nicotinamide ring.
Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent complex.,Ogata K, Yajima Y, Nakamura S, Kaneko R, Goto M, Ohshima T, Yoshimune K Sci Rep. 2018 Apr 10;8(1):5749. doi: 10.1038/s41598-018-24063-1. PMID:29636528[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tomonaga Y, Kaneko R, Goto M, Ohshima T, Yoshimune K. Structural insight into activation of homoserine dehydrogenase from the archaeon Sulfolobus tokodaii via reduction. Biochem Biophys Rep. 2015 Jul 15;3:14-17. doi: 10.1016/j.bbrep.2015.07.006., eCollection 2015 Sep. PMID:29124164 doi:http://dx.doi.org/10.1016/j.bbrep.2015.07.006
- ↑ Ogata K, Yajima Y, Nakamura S, Kaneko R, Goto M, Ohshima T, Yoshimune K. Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent complex. Sci Rep. 2018 Apr 10;8(1):5749. doi: 10.1038/s41598-018-24063-1. PMID:29636528 doi:http://dx.doi.org/10.1038/s41598-018-24063-1
- ↑ Kubota T, Kurihara E, Watanabe K, Ogata K, Kaneko R, Goto M, Ohshima T, Yoshimune K. Conformational changes in the catalytic region are responsible for heat-induced activation of hyperthermophilic homoserine dehydrogenase. Commun Biol. 2022 Jul 14;5(1):704. doi: 10.1038/s42003-022-03656-7. PMID:35835834 doi:http://dx.doi.org/10.1038/s42003-022-03656-7
- ↑ Ogata K, Yajima Y, Nakamura S, Kaneko R, Goto M, Ohshima T, Yoshimune K. Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent complex. Sci Rep. 2018 Apr 10;8(1):5749. doi: 10.1038/s41598-018-24063-1. PMID:29636528 doi:http://dx.doi.org/10.1038/s41598-018-24063-1
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