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| | ==Crystal Structure of succinyl-diaminopimelate desuccinylase from Neisseria meningitidis MC58 in complex with the Inhibitor Captopril== | | ==Crystal Structure of succinyl-diaminopimelate desuccinylase from Neisseria meningitidis MC58 in complex with the Inhibitor Captopril== |
| - | <StructureSection load='4pqa' size='340' side='right' caption='[[4pqa]], [[Resolution|resolution]] 1.78Å' scene=''> | + | <StructureSection load='4pqa' size='340' side='right'caption='[[4pqa]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4pqa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Neimb Neimb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PQA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PQA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4pqa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_MC58 Neisseria meningitidis MC58]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PQA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PQA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8Z:L-CAPTOPRIL'>X8Z</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.78Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dapE, NMB1530 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=122586 NEIMB])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8Z:L-CAPTOPRIL'>X8Z</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Succinyl-diaminopimelate_desuccinylase Succinyl-diaminopimelate desuccinylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.18 3.5.1.18] </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=4pqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pqa OCA], [https://pdbe.org/4pqa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pqa RCSB], [https://www.ebi.ac.uk/pdbsum/4pqa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pqa 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=4pqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pqa OCA], [http://pdbe.org/4pqa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pqa RCSB], [http://www.ebi.ac.uk/pdbsum/4pqa PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DAPE_NEIMB DAPE_NEIMB]] Catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP), forming succinate and LL-2,6-diaminoheptanedioate (DAP), an intermediate involved in the bacterial biosynthesis of lysine and meso-diaminopimelic acid, an essential component of bacterial cell walls (By similarity).[HAMAP-Rule:MF_01690] | + | [https://www.uniprot.org/uniprot/DAPE_NEIMB DAPE_NEIMB] Catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP), forming succinate and LL-2,6-diaminoheptanedioate (DAP), an intermediate involved in the bacterial biosynthesis of lysine and meso-diaminopimelic acid, an essential component of bacterial cell walls (By similarity).[HAMAP-Rule:MF_01690] |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 muM and a measured Ki of 1.8 muM and displayed a dose-responsive antibiotic activity toward Escherichia coli. L-Captopril is also a competitive inhibitor of NmDapE with a Ki of 2.8 muM. To examine the nature of the interaction of L-captopril with the dinuclear active site of DapE, we have obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a thiolate bridge between the two metal ions. Verification of a thiolate-bridged dinuclear complex was obtained by determining the three-dimensional X-ray crystal structure of NmDapE in complex with L-captopril at 1.8 A resolution. Combination of these data provides new insights into binding of L-captopril to the active site of DapE enzymes as well as important inhibitor-active site residue interaction's. Such information is critical for the design of new, potent inhibitors of DapE enzymes.
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| - | Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril.,Starus A, Nocek B, Bennett B, Larrabee JA, Shaw DL, Sae-Lee W, Russo MT, Gillner DM, Makowska-Grzyska M, Joachimiak A, Holz RC Biochemistry. 2015 Aug 11;54(31):4834-44. doi: 10.1021/acs.biochem.5b00475. Epub , 2015 Aug 3. PMID:26186504<ref>PMID:26186504</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4pqa" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Neimb]] | + | [[Category: Large Structures]] |
| - | [[Category: Succinyl-diaminopimelate desuccinylase]] | + | [[Category: Neisseria meningitidis MC58]] |
| - | [[Category: Anderson, W F]] | + | [[Category: Anderson WF]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Holz R]] |
| - | [[Category: Holz, R]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Nocek B]] |
| - | [[Category: Nocek, B]] | + | [[Category: Starus A]] |
| - | [[Category: Starus, A]] | + | |
| - | [[Category: Captopril]]
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| - | [[Category: Csgid]]
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| - | [[Category: Dape]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| - | [[Category: M20 aminopeptidase]]
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| - | [[Category: Metaloenzyme]]
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| - | [[Category: National institute of allergy and infectious disease]]
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| - | [[Category: Niaid]]
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