4mlr: Difference between revisions
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The | ==dihydrodipicolinate synthase from C. jejuni, Y110F mutation with pyruvate and Lysine== | ||
<StructureSection load='4mlr' size='340' side='right'caption='[[4mlr]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4mlr]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Campylobacter_jejuni Campylobacter jejuni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MLR 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KPI:(2S)-2-AMINO-6-[(1-HYDROXY-1-OXO-PROPAN-2-YLIDENE)AMINO]HEXANOIC+ACID'>KPI</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4mlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mlr OCA], [https://pdbe.org/4mlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mlr RCSB], [https://www.ebi.ac.uk/pdbsum/4mlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mlr ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DAPA_CAMJE DAPA_CAMJE] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).[HAMAP-Rule:MF_00418] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and plants, controls a critical step in the biosynthesis of l-lysine and meso-diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS catalyzes the condensation of pyruvate and (S)-aspartate-beta-semialdehyde, forming an unstable product that is dehydrated to dihydrodipicolinate. The tetrameric enzyme is allosterically inhibited by l-lysine, and a better understanding of the allosteric inhibition mechanism is necessary for the design of potent antibacterial therapeutics. Here we describe the high-resolution crystal structures of DHDPS from Campylobacter jejuni with and without its inhibitor bound to the allosteric sites. These structures reveal a role for Y110 in the regulation of the allosteric inhibition by lysine. Mutation of Y110 to phenylalanine results in insensitivity to lysine inhibition, although the mutant crystal structure reveals that lysine does bind in the allosteric site. Comparison of the lysine-bound Y110F structure with wild-type structures reveals that key structural changes due to lysine binding are absent in this mutant. | |||
Tyrosine 110 plays a critical role in regulating the allosteric inhibition of Campylobacter jejuni dihydrodipicolinate synthase by lysine.,Conly CJ, Skovpen YV, Li S, Palmer DR, Sanders DA Biochemistry. 2014 Dec 2;53(47):7396-406. doi: 10.1021/bi5012157. Epub 2014 Nov, 18. PMID:25369463<ref>PMID:25369463</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4mlr" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dihydrodipicolinate synthase|Dihydrodipicolinate synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Campylobacter jejuni]] | |||
[[Category: Large Structures]] | |||
[[Category: Conly CJT]] | |||
Latest revision as of 19:39, 20 September 2023
dihydrodipicolinate synthase from C. jejuni, Y110F mutation with pyruvate and Lysinedihydrodipicolinate synthase from C. jejuni, Y110F mutation with pyruvate and Lysine
Structural highlights
FunctionDAPA_CAMJE Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).[HAMAP-Rule:MF_00418] Publication Abstract from PubMedDihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and plants, controls a critical step in the biosynthesis of l-lysine and meso-diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS catalyzes the condensation of pyruvate and (S)-aspartate-beta-semialdehyde, forming an unstable product that is dehydrated to dihydrodipicolinate. The tetrameric enzyme is allosterically inhibited by l-lysine, and a better understanding of the allosteric inhibition mechanism is necessary for the design of potent antibacterial therapeutics. Here we describe the high-resolution crystal structures of DHDPS from Campylobacter jejuni with and without its inhibitor bound to the allosteric sites. These structures reveal a role for Y110 in the regulation of the allosteric inhibition by lysine. Mutation of Y110 to phenylalanine results in insensitivity to lysine inhibition, although the mutant crystal structure reveals that lysine does bind in the allosteric site. Comparison of the lysine-bound Y110F structure with wild-type structures reveals that key structural changes due to lysine binding are absent in this mutant. Tyrosine 110 plays a critical role in regulating the allosteric inhibition of Campylobacter jejuni dihydrodipicolinate synthase by lysine.,Conly CJ, Skovpen YV, Li S, Palmer DR, Sanders DA Biochemistry. 2014 Dec 2;53(47):7396-406. doi: 10.1021/bi5012157. Epub 2014 Nov, 18. PMID:25369463[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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