3k8c: Difference between revisions
No edit summary |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Complex of Trypanosoma cruzi ribose 5-phosphate isomerase type B with 4-deoxy-4-phospho-D-erythronohydroxamic acid== | |||
<StructureSection load='3k8c' size='340' side='right'caption='[[3k8c]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
or the | <table><tr><td colspan='2'>[[3k8c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi_strain_CL_Brener Trypanosoma cruzi strain CL Brener]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K8C 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]] 2.1Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RES:4-PHOSPHO-D-ERYTHRONOHYDROXAMIC+ACID'>RES</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=3k8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k8c OCA], [https://pdbe.org/3k8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k8c RCSB], [https://www.ebi.ac.uk/pdbsum/3k8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k8c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q4CQE2_TRYCC Q4CQE2_TRYCC] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ribose-5-phosphate isomerase is a key activity of the pentose phosphate pathway. Two unrelated types of sequence/structure were earlier shown to possess this activity, RpiA (present in most organisms) and RpiB (in some bacteria and parasitic protozoa). Here we report enzyme kinetics and crystallographic studies of the RpiB from the human pathogen, Trypanosoma cruzi. Structures of the wild type and a Cys69Ala mutant enzyme, alone or bound to phosphate, d-ribose 5-phosphate, or the inhibitors 4-phospho-d-erythronohydroxamic acid and d-allose 6-phosphate, highlight features of the active site, and show that small conformational changes are linked to binding. Kinetic studies prove that, like the RpiB from Mycobacterium tuberculosis, the T. cruzi enzyme can isomerize d-ribose 5-phosphate effectively, but not the 6-carbon sugar d-allose 6-phosphate; this sugar acts instead as an inhibitor of both enzymes. The behaviour is distinct from that of the more closely related (to T. cruzi RpiB) Escherichia coli enzyme, which can isomerize both types of sugars. The hypothesis that differences in a phosphate-binding loop near the active site were linked to the differences in specificity was tested by construction of a mutant T. cruzi enzyme that has a sequence in this loop more like that of E. coli RpiB; this mutant enzyme gained the ability to act on the 6-carbon sugar. The combined information allows us to distinguish the two types of specificity patterns in other available sequences. Our results provide insights into the action of RpiB enzymes generally, as well as a firm basis for future work in drug design. Structured digital abstract: MINT-8081804, MINT-8081814: TcRpiB (uniprotkb:A1BTJ7) and TcRpiB (uniprotkb:A1BTJ7) bind (MI:0407) by x-ray crystallography (MI:0114). | |||
Structures of type B ribose 5-phosphate isomerase from Trypanosoma cruzi shed light on the determinants of sugar specificity in the structural family.,Stern AL, Naworyta A, Cazzulo JJ, Mowbray SL FEBS J. 2010 Dec 27. doi: 10.1111/j.1742-4658.2010.07999.x. PMID:21205211<ref>PMID:21205211</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3k8c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ribose-5-phosphate isomerase 3D structures|Ribose-5-phosphate isomerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[ | [[Category: Trypanosoma cruzi strain CL Brener]] | ||
[[Category: Mowbray SL]] | |||
== | [[Category: Naworyta A]] | ||
< | [[Category: Stern AL]] | ||
[[Category: | |||
[[Category: Trypanosoma cruzi]] | |||
[[Category: Mowbray | |||
[[Category: Naworyta | |||
[[Category: Stern | |||
Latest revision as of 11:11, 6 September 2023
Complex of Trypanosoma cruzi ribose 5-phosphate isomerase type B with 4-deoxy-4-phospho-D-erythronohydroxamic acidComplex of Trypanosoma cruzi ribose 5-phosphate isomerase type B with 4-deoxy-4-phospho-D-erythronohydroxamic acid
Structural highlights
FunctionPublication Abstract from PubMedRibose-5-phosphate isomerase is a key activity of the pentose phosphate pathway. Two unrelated types of sequence/structure were earlier shown to possess this activity, RpiA (present in most organisms) and RpiB (in some bacteria and parasitic protozoa). Here we report enzyme kinetics and crystallographic studies of the RpiB from the human pathogen, Trypanosoma cruzi. Structures of the wild type and a Cys69Ala mutant enzyme, alone or bound to phosphate, d-ribose 5-phosphate, or the inhibitors 4-phospho-d-erythronohydroxamic acid and d-allose 6-phosphate, highlight features of the active site, and show that small conformational changes are linked to binding. Kinetic studies prove that, like the RpiB from Mycobacterium tuberculosis, the T. cruzi enzyme can isomerize d-ribose 5-phosphate effectively, but not the 6-carbon sugar d-allose 6-phosphate; this sugar acts instead as an inhibitor of both enzymes. The behaviour is distinct from that of the more closely related (to T. cruzi RpiB) Escherichia coli enzyme, which can isomerize both types of sugars. The hypothesis that differences in a phosphate-binding loop near the active site were linked to the differences in specificity was tested by construction of a mutant T. cruzi enzyme that has a sequence in this loop more like that of E. coli RpiB; this mutant enzyme gained the ability to act on the 6-carbon sugar. The combined information allows us to distinguish the two types of specificity patterns in other available sequences. Our results provide insights into the action of RpiB enzymes generally, as well as a firm basis for future work in drug design. Structured digital abstract: MINT-8081804, MINT-8081814: TcRpiB (uniprotkb:A1BTJ7) and TcRpiB (uniprotkb:A1BTJ7) bind (MI:0407) by x-ray crystallography (MI:0114). Structures of type B ribose 5-phosphate isomerase from Trypanosoma cruzi shed light on the determinants of sugar specificity in the structural family.,Stern AL, Naworyta A, Cazzulo JJ, Mowbray SL FEBS J. 2010 Dec 27. doi: 10.1111/j.1742-4658.2010.07999.x. PMID:21205211[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||