2ojp: Difference between revisions
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< | ==The crystal structure of a dimeric mutant of Dihydrodipicolinate synthase from E.coli- DHDPS-L197Y== | ||
<StructureSection load='2ojp' size='340' side='right'caption='[[2ojp]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ojp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OJP 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]] 1.7Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KGC:N~6~-[(2R)-2-CARBOXY-5-OXOTETRAHYDROFURAN-2-YL]-L-LYSINE'>KGC</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=2ojp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ojp OCA], [https://pdbe.org/2ojp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ojp RCSB], [https://www.ebi.ac.uk/pdbsum/2ojp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ojp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DAPA_ECOLI DAPA_ECOLI] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).<ref>PMID:20503968</ref> <ref>PMID:8993314</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oj/2ojp_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ojp ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dihydrodipicolinate synthase (DHDPS) is an essential enzyme in (S)-lysine biosynthesis and an important antibiotic target. All X-ray crystal structures solved to date reveal a homotetrameric enzyme. In order to explore the role of this quaternary structure, dimeric variants of Escherichia coli DHDPS were engineered and their properties were compared to those of the wild-type tetrameric form. X-ray crystallography reveals that the active site is not disturbed when the quaternary structure is disrupted. However, the activity of the dimeric enzymes in solution is substantially reduced, and a tetrahedral adduct of a substrate analogue is observed to be trapped at the active site in the crystal form. Remarkably, heating the dimeric enzymes increases activity. We propose that the homotetrameric structure of DHDPS reduces dynamic fluctuations present in the dimeric forms and increases specificity for the first substrate, pyruvate. By restricting motion in a key catalytic motif, a competing, non-productive reaction with a substrate analogue is avoided. Small-angle X-ray scattering and mutagenesis data, together with a B-factor analysis of the crystal structures, support this hypothesis and lead to the suggestion that in at least some cases, the evolution of quaternary enzyme structures might serve to optimise the dynamic properties of the protein subunits. | |||
Evolution of quaternary structure in a homotetrameric enzyme.,Griffin MD, Dobson RC, Pearce FG, Antonio L, Whitten AE, Liew CK, Mackay JP, Trewhella J, Jameson GB, Perugini MA, Gerrard JA J Mol Biol. 2008 Jul 18;380(4):691-703. Epub 2008 May 22. PMID:18556019<ref>PMID:18556019</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ojp" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Dihydrodipicolinate synthase|Dihydrodipicolinate synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Antonio | [[Category: Antonio L]] | ||
[[Category: Dobson | [[Category: Dobson RCJ]] | ||
[[Category: Gerrard | [[Category: Gerrard JA]] | ||
[[Category: Griffin | [[Category: Griffin MDW]] | ||
[[Category: Jameson | [[Category: Jameson GB]] | ||
[[Category: Perugini | [[Category: Perugini MA]] | ||
Latest revision as of 03:19, 28 December 2023
The crystal structure of a dimeric mutant of Dihydrodipicolinate synthase from E.coli- DHDPS-L197YThe crystal structure of a dimeric mutant of Dihydrodipicolinate synthase from E.coli- DHDPS-L197Y
Structural highlights
FunctionDAPA_ECOLI Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDihydrodipicolinate synthase (DHDPS) is an essential enzyme in (S)-lysine biosynthesis and an important antibiotic target. All X-ray crystal structures solved to date reveal a homotetrameric enzyme. In order to explore the role of this quaternary structure, dimeric variants of Escherichia coli DHDPS were engineered and their properties were compared to those of the wild-type tetrameric form. X-ray crystallography reveals that the active site is not disturbed when the quaternary structure is disrupted. However, the activity of the dimeric enzymes in solution is substantially reduced, and a tetrahedral adduct of a substrate analogue is observed to be trapped at the active site in the crystal form. Remarkably, heating the dimeric enzymes increases activity. We propose that the homotetrameric structure of DHDPS reduces dynamic fluctuations present in the dimeric forms and increases specificity for the first substrate, pyruvate. By restricting motion in a key catalytic motif, a competing, non-productive reaction with a substrate analogue is avoided. Small-angle X-ray scattering and mutagenesis data, together with a B-factor analysis of the crystal structures, support this hypothesis and lead to the suggestion that in at least some cases, the evolution of quaternary enzyme structures might serve to optimise the dynamic properties of the protein subunits. Evolution of quaternary structure in a homotetrameric enzyme.,Griffin MD, Dobson RC, Pearce FG, Antonio L, Whitten AE, Liew CK, Mackay JP, Trewhella J, Jameson GB, Perugini MA, Gerrard JA J Mol Biol. 2008 Jul 18;380(4):691-703. Epub 2008 May 22. PMID:18556019[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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