3i7s
From Proteopedia
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| - | [[ | + | ==Dihydrodipicolinate synthase mutant - K161A - with the substrate pyruvate bound in the active site.== |
| + | <StructureSection load='3i7s' size='340' side='right' caption='[[3i7s]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3i7s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_k-12 Escherichia coli k-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I7S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I7S FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3i7q|3i7q]], [[3i7r|3i7r]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b2478, dapA, JW2463 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 Escherichia coli K-12])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrodipicolinate_synthase Dihydrodipicolinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.52 4.2.1.52] </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=3i7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i7s RCSB], [http://www.ebi.ac.uk/pdbsum/3i7s PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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/i7/3i7s_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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52), a validated antibiotic target, catalyses the first committed step in the lysine biosynthetic pathway: the condensation reaction between (S)-aspartate beta-semialdehyde [(S)-ASA] and pyruvate via the formation of a Schiff base intermediate between pyruvate and the absolutely conserved active-site lysine. Escherichia coli DHDPS mutants K161A and K161R of the active-site lysine were characterised for the first time. Unexpectedly, the mutant enzymes were still catalytically active, albeit with a significant decrease in activity. The k(cat) values for DHDPS-K161A and DHDPS-K161R were 0.06 +/- 0.02 s(-1) and 0.16 +/- 0.06 s(-1) respectively, compared to 45 +/- 3 s(-1) for the wild-type enzyme. Remarkably, the K(M) values for pyruvate increased by only 3-fold for DHDPS-K161A and DHDPS-K161R (0.45 +/- 0.04 mM and 0.57 +/- 0.06 mM, compared to 0.15 +/- 0.01 mM for the wild-type DHDPS), while the K(M) values for (S)-ASA remained the same for DHDPS-K161R (0.12 +/- 0.01 mM) and increased by only 2-fold for DHDPS-K161A (0.23 +/- 0.02 mM) and the K(i) for lysine was unchanged. The X-ray crystal structures of DHDPS-K161A and DHDPS-K161R were solved at resolutions of 2.0 and 2.1 A respectively and showed no changes in their secondary or tertiary structures when compared to the wild-type structure. The crystal structure of DHDPS-K161A with pyruvate bound at the active site was solved at a resolution of 2.3 A and revealed a defined binding pocket for pyruvate that is thus not dependent upon lysine 161. Taken together with ITC and NMR data, it is concluded that although lysine 161 is important in the wild-type DHDPS-catalysed reaction, it is not absolutely essential for catalysis. | ||
| - | + | How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase?,Soares da Costa TP, Muscroft-Taylor AC, Dobson RC, Devenish SR, Jameson GB, Gerrard JA Biochimie. 2010 Jul;92(7):837-45. Epub 2010 Mar 29. PMID:20353808<ref>PMID:20353808</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
| - | *[[Dihydrodipicolinate | + | *[[Dihydrodipicolinate synthase|Dihydrodipicolinate synthase]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Dihydrodipicolinate synthase]] | [[Category: Dihydrodipicolinate synthase]] | ||
[[Category: Escherichia coli k-12]] | [[Category: Escherichia coli k-12]] | ||
| - | [[Category: Costa, T P.Soares da | + | [[Category: Costa, T P.Soares da]] |
| - | [[Category: Dobson, R C.J | + | [[Category: Dobson, R C.J]] |
| - | [[Category: Gerrard, J A | + | [[Category: Gerrard, J A]] |
| - | [[Category: Jameson, G B | + | [[Category: Jameson, G B]] |
[[Category: Amino-acid biosynthesis]] | [[Category: Amino-acid biosynthesis]] | ||
[[Category: Diaminopimelate biosynthesis]] | [[Category: Diaminopimelate biosynthesis]] | ||
Revision as of 12:47, 5 January 2015
Dihydrodipicolinate synthase mutant - K161A - with the substrate pyruvate bound in the active site.
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