4ppz
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ppz]] 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=4PPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ppz]] 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=4PPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPZ FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4ppz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppz OCA], [https://pdbe.org/4ppz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppz RCSB], [https://www.ebi.ac.uk/pdbsum/4ppz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppz ProSAT]</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=4ppz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppz OCA], [https://pdbe.org/4ppz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppz RCSB], [https://www.ebi.ac.uk/pdbsum/4ppz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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] | [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;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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. | ||
| - | |||
| - | 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> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4ppz" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of zinc-bound succinyl-diaminopimelate desuccinylase from Neisseria meningitidis MC58
| |||||||||||
