2oo0: Difference between revisions
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<StructureSection load='2oo0' size='340' side='right'caption='[[2oo0]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='2oo0' size='340' side='right'caption='[[2oo0]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2oo0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2oo0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OO0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=N2P:PENTANE-1,5-DIAMINE'>N2P</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=XAP:3-AMINOOXY-1-AMINOPROPANE'>XAP</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=N2P:PENTANE-1,5-DIAMINE'>N2P</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=XAP:3-AMINOOXY-1-AMINOPROPANE'>XAP</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=2oo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oo0 OCA], [https://pdbe.org/2oo0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oo0 RCSB], [https://www.ebi.ac.uk/pdbsum/2oo0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oo0 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=2oo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oo0 OCA], [https://pdbe.org/2oo0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oo0 RCSB], [https://www.ebi.ac.uk/pdbsum/2oo0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oo0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/DCOR_HUMAN DCOR_HUMAN] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Al-Karadaghi S]] | |||
[[Category: Al-Karadaghi | [[Category: Dufe VT]] | ||
[[Category: Dufe | [[Category: Heby O]] | ||
[[Category: Heby | [[Category: Ingner D]] | ||
[[Category: Ingner | [[Category: Khomutov AR]] | ||
[[Category: Khomutov | [[Category: Persson L]] | ||
[[Category: Persson | |||
Latest revision as of 13:45, 30 August 2023
A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 3-aminooxy-1-aminopropaneA structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 3-aminooxy-1-aminopropane
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe critical role of polyamines in key processes such as cell growth, differentiation and macromolecular synthesis makes the enzymes involved in their synthesis potential targets in the treatment of certain types of cancer and parasitic diseases. Here we present a study on the inhibition of human and Leishmania donovani ODC (ornithine decarboxylase), the first committed enzyme in the polyamine biosynthesis pathway, by APA (1-amino-oxy-3-aminopropane). The present study shows APA to be a potent inhibitor of both human and L. donovani ODC with a K(i) value of around 1.0 nM. We also show that L. donovani ODC binds the substrate, the co-enzyme pyridoxal 5'-phosphate and the irreversible inhibitor alpha-difluoromethylornithine (a curative agent of West African sleeping sickness) with less affinity than human ODC. We have also determined the three-dimensional structure of human ODC in complex with APA, which revealed the mode of the inhibitor binding to the enzyme. In contrast with earlier reports, the structure showed no indication of oxime formation between APA and PLP (pyridoxal 5'-phosphate). Homology modelling suggests a similar mode of binding of APA to L. donovani ODC. A comparison of the ODC-APA-PLP structure with earlier ODC structures also shows that the protease-sensitive loop (residues 158-168) undergoes a large conformational change and covers the active site of the protein. The understanding of the structural mode of APA binding may constitute the basis for the development of more specific inhibitors of L. donovani ODC. A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane.,Dufe VT, Ingner D, Heby O, Khomutov AR, Persson L, Al-Karadaghi S Biochem J. 2007 Jul 15;405(2):261-8. PMID:17407445[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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