5ls7: Difference between revisions

Revision as of 10:48, 12 August 2020

Complex of wild type E. coli alpha aspartate decarboxylase with its processing factor PanZ

Structural highlights

5ls7 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	74C, ACO, CO2, GOL, MG, PEG, SCN
NonStd Res:	CSO, PVO
Activity:	Aspartate 1-decarboxylase, with EC number 4.1.1.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PAND_ECOLI] Catalyzes the pyruvoyl-dependent decarboxylation of aspartate to produce beta-alanine.^[1] [PANZ_ECOLI] Controls both the activation and catalytic activity of PanD in a coenzyme A (CoA)-dependent fashion. Binding of CoA or a derivative to PanZ leads to interaction with PanD, which promotes the processing and activation of pro-PanD, and subsequent substrate-mediated inhibition of the active form of PanD (PubMed:23170229, PubMed:25910242). Inhibition of PanD activity is probably the primary metabolic role of PanZ, allowing negative feedback regulation of pantothenate biosynthesis by CoA (PubMed:25910242).^[2] ^[3]

Publication Abstract from PubMed

The antimetabolite pentyl pantothenamide has broad spectrum antibiotic activity but exhibits enhanced activity against Escherichia coli. The PanDZ complex has been proposed to regulate the pantothenate biosynthetic pathway in E. coli by limiting the supply of beta-alanine in response to coenzyme A concentration. We show that formation of such a complex between activated aspartate decarboxylase (PanD) and PanZ leads to sequestration of the pyruvoyl cofactor as a ketone hydrate and demonstrate that both PanZ overexpression-linked beta-alanine auxotrophy and pentyl pantothenamide toxicity are due to formation of this complex. This both demonstrates that the PanDZ complex regulates pantothenate biosynthesis in a cellular context and validates the complex as a target for antibiotic development.

The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ.AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan).,Arnott ZLP, Nozaki S, Monteiro DCF, Morgan HE, Pearson AR, Niki H, Webb ME Biochemistry. 2017 Sep 7. doi: 10.1021/acs.biochem.7b00509. PMID:28832133^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cronan JE Jr. Beta-alanine synthesis in Escherichia coli. J Bacteriol. 1980 Mar;141(3):1291-7. PMID:6767707
↑ Nozaki S, Webb ME, Niki H. An activator for pyruvoyl-dependent l-aspartate alpha-decarboxylase is conserved in a small group of the gamma-proteobacteria including Escherichia coli. Microbiologyopen. 2012 Sep;1(3):298-310. doi: 10.1002/mbo3.34. Epub 2012 Aug 14. PMID:23170229 doi:https://dx.doi.org/10.1002/mbo3.34
↑ Monteiro DC, Patel V, Bartlett CP, Nozaki S, Grant TD, Gowdy JA, Thompson GS, Kalverda AP, Snell EH, Niki H, Pearson AR, Webb ME. The Structure of the PanD/PanZ Protein Complex Reveals Negative Feedback Regulation of Pantothenate Biosynthesis by Coenzyme A. Chem Biol. 2015 Apr 23;22(4):492-503. doi: 10.1016/j.chembiol.2015.03.017. PMID:25910242 doi:https://dx.doi.org/10.1016/j.chembiol.2015.03.017
↑ Arnott ZLP, Nozaki S, Monteiro DCF, Morgan HE, Pearson AR, Niki H, Webb ME. The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ.AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan). Biochemistry. 2017 Sep 7. doi: 10.1021/acs.biochem.7b00509. PMID:28832133 doi:https://dx.doi.org/10.1021/acs.biochem.7b00509

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Cronan JE Jr. Beta-alanine synthesis in Escherichia coli. J Bacteriol. 1980 Mar;141(3):1291-7. PMID:6767707

[2] Nozaki S, Webb ME, Niki H. An activator for pyruvoyl-dependent l-aspartate alpha-decarboxylase is conserved in a small group of the gamma-proteobacteria including Escherichia coli. Microbiologyopen. 2012 Sep;1(3):298-310. doi: 10.1002/mbo3.34. Epub 2012 Aug 14. PMID:23170229 doi:https://dx.doi.org/10.1002/mbo3.34

[3] Monteiro DC, Patel V, Bartlett CP, Nozaki S, Grant TD, Gowdy JA, Thompson GS, Kalverda AP, Snell EH, Niki H, Pearson AR, Webb ME. The Structure of the PanD/PanZ Protein Complex Reveals Negative Feedback Regulation of Pantothenate Biosynthesis by Coenzyme A. Chem Biol. 2015 Apr 23;22(4):492-503. doi: 10.1016/j.chembiol.2015.03.017. PMID:25910242 doi:https://dx.doi.org/10.1016/j.chembiol.2015.03.017

[4] Arnott ZLP, Nozaki S, Monteiro DCF, Morgan HE, Pearson AR, Niki H, Webb ME. The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ.AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan). Biochemistry. 2017 Sep 7. doi: 10.1021/acs.biochem.7b00509. PMID:28832133 doi:https://dx.doi.org/10.1021/acs.biochem.7b00509

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==Complex of wild type E. coli alpha aspartate decarboxylase with its processing factor PanZ==
-<StructureSection load='5ls7' size='340' side='right' caption='[[5ls7]], [[Resolution|resolution]] 1.16&Aring;' scene=''>
+<StructureSection load='5ls7' size='340' side='right'caption='[[5ls7]], [[Resolution|resolution]] 1.16&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ls7]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LS7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ls7]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LS7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LS7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=74C:methyl+radical'>74C</scene>, <scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=74C:methyl+radical'>74C</scene>, <scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=PVO:'>PVO</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_1-decarboxylase Aspartate 1-decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.11 4.1.1.11] </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=5ls7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ls7 OCA], [http://pdbe.org/5ls7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ls7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ls7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ls7 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ls7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ls7 OCA], [http://pdbe.org/5ls7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ls7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ls7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ls7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5ls7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aspartate decarboxylase 3D structures|Aspartate decarboxylase 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Aspartate 1-decarboxylase]]
+[[Category: Large Structures]]
 [[Category: Monteiro, D C.F]]
 [[Category: Pearson, A R]]

5ls7: Difference between revisions

Revision as of 10:48, 12 August 2020

Complex of wild type E. coli alpha aspartate decarboxylase with its processing factor PanZ

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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