3pf3 | pdb_00003pf3

Crystal structure of a mutant (C202A) of Triosephosphate isomerase from Giardia lamblia derivatized with MMTS

spinqualitylabelsall models 3pf3, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3pf3 is a 1 chain structure with sequence from Giardia intestinalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, GOL, SO4 NonStd Res: SCH Related: 2dp3 Gene: GLTIM (Giardia intestinalis) Activity: Triose-phosphate isomerase, with EC number 5.3.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Giardiasis, the most prevalent intestinal parasitosis in humans, is caused by Giardia lamblia. Current drug therapies have adverse effects on the host, and resistant strains against these drugs have been reported, demonstrating an urgent need to design more specific antigiardiasic drugs. ATP production in G. lamblia depends mainly on glycolysis; therefore, all enzymes of this pathway have been proposed as potential drug targets. We previously demonstrated that the glycolytic enzyme triosephosphate isomerase from G. lamblia (GlTIM), could be completely inactivated by low micromolar concentrations of thiol-reactive compounds, whereas, in the same conditions, the activity of human TIM (HuTIM) was almost unaltered. We found that the chemical modification (derivatization) of at least one Cys, of the five Cys residues per monomer in GlTIM, causes this inactivation. In this study, structural and functional studies were performed to describe the molecular mechanism of GlTIM inactivation by thiol-reactive compounds. We found that the Cys222 derivatization is responsible for GlTIM inactivation; this information is relevant because HuTIM has a Cys residue in an equivalent position (Cys217). GlTIM inactivation is associated with a decrease in ligand affinity, which affects the entropic component of ligand binding. In summary, this work describes a mechanism of inactivation that has not been previously reported for TIMs from other parasites and furthermore, we show that the difference in reactivity between the Cys222 in GlTIM and the Cys217 in HuTIM, indicates that the surrounding environment of each Cys residue has unique structural differences that can be exploited to design specific antigiardiasic drugs. Proteins 2011;. (c) 2011 Wiley-Liss, Inc. Determining the molecular mechanism of inactivation by chemical modification of triosephosphate isomerase from the human parasite Giardia lamblia: A study for antiparasitic drug design.,Enriquez-Flores S, Rodriguez-Romero A, Hernandez-Alcantara G, Oria-Hernandez J, Gutierrez-Castrellon P, Perez-Hernandez G, Mora Ide L, Castillo-Villanueva A, Garcia-Torres I, Mendez ST, Gomez-Manzo S, Torres-Arroyo A, Lopez-Velazquez G, Reyes-Vivas H Proteins. 2011 Sep;79(9):2711-24. doi: 10.1002/prot.23100. Epub 2011 Jul, 22. PMID:21786322 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Triose Phosphate Isomerase

Proteopedia Page Contributors and Editors (what is this?)

OCA