View source for 4aib


==Crystal Structure of Ornithine Decarboxylase from Entamoeba histolytica.==
<StructureSection load='4aib' size='340' side='right'caption='[[4aib]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4aib]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica_HM-1:IMSS Entamoeba histolytica HM-1:IMSS]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AIB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AIB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.87&#8491;</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=4aib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aib OCA], [https://pdbe.org/4aib PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aib RCSB], [https://www.ebi.ac.uk/pdbsum/4aib PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aib ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q58P26_ENTHI Q58P26_ENTHI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Polyamine biosynthetic pathway is a validated therapeutic target for large number of infectious diseases including cancer, giardiasis and African sleeping sickness, etc. alpha-Difluoromethylornithine (DFMO), a potent drug used for the treatment of African sleeping sickness is an irreversible inhibitor of ornithine decarboxylase (ODC), the first rate limiting enzyme of polyamine biosynthesis. The enzyme ODC of E. histolytica (EhODC) has been reported to exhibit resistance towards DFMO. METHODOLOGY/PRINCIPAL FINDING: The basis for insensitivity towards DFMO was investigated by structural analysis of EhODC and conformational modifications at the active site. Here, we report cloning, purification and crystal structure determination of C-terminal truncated Entamoeba histolytica ornithine decarboxylase (EhODCDelta15). Structure was determined by molecular replacement method and refined to 2.8 A resolution. The orthorhombic crystal exhibits P2(1)2(1)2(1) symmetry with unit cell parameters a = 76.66, b = 119.28, c = 179.28 A. Functional as well as evolutionary relations of EhODC with other ODC homologs were predicted on the basis of sequence analysis, phylogeny and structure. CONCLUSIONS/SIGNIFICANCE: We determined the tetrameric crystal structure of EhODCDelta15, which exists as a dimer in solution. Insensitivity towards DFMO is due to substitution of key substrate binding residues in active site pocket. Additionally, a few more substitutions similar to antizyme inhibitor (AZI), a non-functional homologue of ODCs, were identified in the active site. Here, we establish the fact that EhODC sequence has conserved PLP binding residues; in contrast few substrate binding residues are mutated similar to AZI. Further sequence analysis and structural studies revealed that EhODC may represent as an evolutionary bridge between active decarboxylase and inactive AZI.

Structural Insight into DFMO Resistant Ornithine Decarboxylase from Entamoeba histolytica: An Inkling to Adaptive Evolution.,Preeti, Tapas S, Kumar P, Madhubala R, Tomar S PLoS One. 2013;8(1):e53397. doi: 10.1371/journal.pone.0053397. Epub 2013 Jan 11. PMID:23326423<ref>PMID:23326423</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4aib" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ornithine decarboxylase|Ornithine decarboxylase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Entamoeba histolytica HM-1:IMSS]]
[[Category: Large Structures]]
[[Category: Kumar P]]
[[Category: Preeti P]]
[[Category: Tomar S]]