6dss: Difference between revisions

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<StructureSection load='6dss' size='340' side='right'caption='[[6dss]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='6dss' size='340' side='right'caption='[[6dss]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6dss]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DSS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DSS FirstGlance]. <br>
<table><tr><td colspan='2'>[[6dss]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DSS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</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]] 2.599&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2za3|2za3]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] </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=6dss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dss OCA], [https://pdbe.org/6dss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dss RCSB], [https://www.ebi.ac.uk/pdbsum/6dss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dss 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=6dss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dss OCA], [http://pdbe.org/6dss PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dss RCSB], [http://www.ebi.ac.uk/pdbsum/6dss PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dss ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8T6J6_PLAFA Q8T6J6_PLAFA]
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Orotidine 5'-monophoshate decarboxylase (OMPDC) catalyses the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP). Here, we report the X-ray analysis of apo, substrate or product-complex forms of OMPDC from Plasmodium falciparum (PfOMPDC) at 2.7, 2.65 and 2.65 A, respectively. The structural analysis provides the substrate recognition mechanism with dynamic structural changes, as well as the rearrangement of the hydrogen bond array at the active site. The structural basis of substrate or product binding to PfOMPDC will help to uncover the decarboxylation mechanism and facilitate structure-based optimization of antimalarial drugs.
The development of antimalarial drugs remains a public health priority, and the orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) has great potential as a drug target. The crystallization of PfOMPDC with substrate bound represents an important advance for structure-based drug-design efforts [Tokuoka et al. (2008), J. Biochem. 143, 69-78]. The complex of the enzyme bound to the substrate OMP (PDB entry 2za1) would be of particular utility in this regard. However, re-refinement of this structure of the Michaelis complex shows that the bound ligand is the product rather than the substrate. Here, the re-refinement of a set of three structures, the apo enzyme and two versions of the product-bound form (PDB entries 2za1, 2za2 and 2za3), is reported. The improved geometry and fit of these structures to the observed electron density will enhance their utility in antimalarial drug design.


Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium falciparum OMP decarboxylase.,Tokuoka K, Kusakari Y, Krungkrai SR, Matsumura H, Kai Y, Krungkrai J, Horii T, Inoue T J Biochem. 2008 Jan;143(1):69-78. Epub 2007 Nov 1. PMID:17981823<ref>PMID:17981823</ref>
Re-refinement of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase provides a clearer picture of an important malarial drug target.,Novak WRP, West KHJ, Kirkman LMD, Brandt GS Acta Crystallogr F Struct Biol Commun. 2018 Oct 1;74(Pt 10):664-668. doi:, 10.1107/S2053230X18010610. Epub 2018 Sep 21. PMID:30279319<ref>PMID:30279319</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Orotidine-5'-phosphate decarboxylase]]
[[Category: Plasmodium falciparum]]
[[Category: Brandt, G S]]
[[Category: Brandt GS]]
[[Category: Novak, W R.P]]
[[Category: Novak WRP]]
[[Category: Complex]]
[[Category: Lyase]]
[[Category: P falciparum]]

Latest revision as of 09:13, 11 October 2023

Re-refinement of P. falciparum orotidine 5'-monophosphate decarboxylaseRe-refinement of P. falciparum orotidine 5'-monophosphate decarboxylase

Structural highlights

6dss is a 2 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.599Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8T6J6_PLAFA

Publication Abstract from PubMed

The development of antimalarial drugs remains a public health priority, and the orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) has great potential as a drug target. The crystallization of PfOMPDC with substrate bound represents an important advance for structure-based drug-design efforts [Tokuoka et al. (2008), J. Biochem. 143, 69-78]. The complex of the enzyme bound to the substrate OMP (PDB entry 2za1) would be of particular utility in this regard. However, re-refinement of this structure of the Michaelis complex shows that the bound ligand is the product rather than the substrate. Here, the re-refinement of a set of three structures, the apo enzyme and two versions of the product-bound form (PDB entries 2za1, 2za2 and 2za3), is reported. The improved geometry and fit of these structures to the observed electron density will enhance their utility in antimalarial drug design.

Re-refinement of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase provides a clearer picture of an important malarial drug target.,Novak WRP, West KHJ, Kirkman LMD, Brandt GS Acta Crystallogr F Struct Biol Commun. 2018 Oct 1;74(Pt 10):664-668. doi:, 10.1107/S2053230X18010610. Epub 2018 Sep 21. PMID:30279319[1]

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

See Also

References

  1. Novak WRP, West KHJ, Kirkman LMD, Brandt GS. Re-refinement of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase provides a clearer picture of an important malarial drug target. Acta Crystallogr F Struct Biol Commun. 2018 Oct 1;74(Pt 10):664-668. PMID:30279319 doi:10.1107/S2053230X18010610

6dss, resolution 2.60Å

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