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| | ==Crystal structure of diaminopimelate epimerase Y268A mutant from Escherichia coli== | | ==Crystal structure of diaminopimelate epimerase Y268A mutant from Escherichia coli== |
| - | <StructureSection load='4ik0' size='340' side='right' caption='[[4ik0]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='4ik0' size='340' side='right'caption='[[4ik0]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ik0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IK0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ik0]] is a 2 chain structure with sequence from [https://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=4IK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IK0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ijz|4ijz]]</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=4ik0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ik0 OCA], [https://pdbe.org/4ik0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ik0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ik0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ik0 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dapF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diaminopimelate_epimerase Diaminopimelate epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.7 5.1.1.7] </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=4ik0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ik0 OCA], [http://pdbe.org/4ik0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ik0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ik0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ik0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DAPF_ECOLI DAPF_ECOLI]] Catalyzes the stereoinversion of LL-2,6-diaminoheptanedioate (L,L-DAP) to meso-diaminoheptanedioate (meso-DAP), a precursor of L-lysine and an essential component of the bacterial peptidoglycan. Only accepts DAP isomers with the L configuration.<ref>PMID:6378903</ref> <ref>PMID:3031013</ref> <ref>PMID:3042781</ref> | + | [https://www.uniprot.org/uniprot/DAPF_ECOLI DAPF_ECOLI] Catalyzes the stereoinversion of LL-2,6-diaminoheptanedioate (L,L-DAP) to meso-diaminoheptanedioate (meso-DAP), a precursor of L-lysine and an essential component of the bacterial peptidoglycan. Only accepts DAP isomers with the L configuration.<ref>PMID:6378903</ref> <ref>PMID:3031013</ref> <ref>PMID:3042781</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: Diaminopimelate epimerase]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecoli]] | + | [[Category: Large Structures]] |
| - | [[Category: Dobson, R C.J]] | + | [[Category: Dobson RCJ]] |
| - | [[Category: Hor, L]] | + | [[Category: Hor L]] |
| - | [[Category: Hutton, C A]] | + | [[Category: Hutton CA]] |
| - | [[Category: Perugini, M A]] | + | [[Category: Perugini MA]] |
| - | [[Category: Cytosol]]
| + | |
| - | [[Category: Dap epimerase-like]]
| + | |
| - | [[Category: Isomerase]]
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| Structural highlights
Function
DAPF_ECOLI Catalyzes the stereoinversion of LL-2,6-diaminoheptanedioate (L,L-DAP) to meso-diaminoheptanedioate (meso-DAP), a precursor of L-lysine and an essential component of the bacterial peptidoglycan. Only accepts DAP isomers with the L configuration.[1] [2] [3]
Publication Abstract from PubMed
Diaminopimelate (DAP) epimerase is involved in the biosynthesis of meso-DAP and lysine, which are important precursors for the synthesis of peptidoglycan, housekeeping proteins and virulence factors in bacteria. Accordingly, DAP epimerase is a promising antimicrobial target. Previous studies report that bacterial DAP epimerase exists as a monomeric enzyme. However, we show using analytical ultracentrifugation, X-ray crystallography and enzyme kinetic analyses that DAP epimerase from Escherichia coli exists as a functional dimer in solution and the crystal state. Furthermore, the 2.0 Angstrom X-ray crystal structure of the E. coli DAP epimerase dimer shows for the first time that the enzyme exists in an open, active conformation. The importance of dimerization was subsequently probed by employing site-directed mutagenesis to generate a monomeric mutant (Y268A). Our studies show that Y268A is catalytically inactive, thus demonstrating that dimerization of DAP epimerase is essential for catalysis. Molecular dynamics simulations indicate that the DAP epimerase monomer is inherently more flexible than the dimer, suggesting that dimerization optimizes protein dynamics to support function. Our findings offer insight into the development of novel antimicrobial agents targeting the dimeric antibiotic target, DAP epimerase.
Dimerization of Bacterial Diaminopimelate Epimerase is Essential for Catalysis.,Hor L, Dobson RC, Downton MT, Wagner J, Hutton CA, Perugini MA J Biol Chem. 2013 Feb 19. PMID:23426375[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wiseman JS, Nichols JS. Purification and properties of diaminopimelic acid epimerase from Escherichia coli. J Biol Chem. 1984 Jul 25;259(14):8907-14. PMID:6378903
- ↑ Richaud C, Higgins W, Mengin-Lecreulx D, Stragier P. Molecular cloning, characterization, and chromosomal localization of dapF, the Escherichia coli gene for diaminopimelate epimerase. J Bacteriol. 1987 Apr;169(4):1454-9. PMID:3031013
- ↑ Lam LK, Arnold LD, Kalantar TH, Kelland JG, Lane-Bell PM, Palcic MM, Pickard MA, Vederas JC. Analogs of diaminopimelic acid as inhibitors of meso-diaminopimelate dehydrogenase and LL-diaminopimelate epimerase. J Biol Chem. 1988 Aug 25;263(24):11814-9. PMID:3042781
- ↑ Hor L, Dobson RC, Downton MT, Wagner J, Hutton CA, Perugini MA. Dimerization of Bacterial Diaminopimelate Epimerase is Essential for Catalysis. J Biol Chem. 2013 Feb 19. PMID:23426375 doi:http://dx.doi.org/10.1074/jbc.M113.450148
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