3k8c | pdb_00003k8c

Complex of Trypanosoma cruzi ribose 5-phosphate isomerase type B with 4-deoxy-4-phospho-D-erythronohydroxamic acid

spinqualitylabelsall models 3k8c, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3k8c is a 2 chain structure with sequence from Trycc. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: RES Related: 3k7o, 3k7s, 3k7p Gene: 110984573 (TRYCC) Activity: Ribose-5-phosphate isomerase, with EC number 5.3.1.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribose-5-phosphate isomerase 3D structures

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