7crz

Crystal structure of human glucose transporter GLUT3 bound with C3361

spinqualitylabelsall models 7crz, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7crz is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: F00, OLC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GTR3_HUMAN Huntington disease. Function GTR3_HUMAN Facilitative glucose transporter. Probably a neuronal glucose transporter. Publication Abstract from PubMed Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a "selective starvation" strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-A resolution. Structural comparison between the present hGLUT3-C3361 and our previously reported PfHT1-C3361 confirmed the unique inhibitor binding-induced pocket in PfHT1. We then designed small molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure-activity relationship studies, the TH-PF series was identified to selectively inhibit PfHT1 over hGLUT1 and potent against multiple strains of the blood-stage P. falciparum Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously target the orthosteric and allosteric sites of a transporter. Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents.,Huang J, Yuan Y, Zhao N, Pu D, Tang Q, Zhang S, Luo S, Yang X, Wang N, Xiao Y, Zhang T, Liu Z, Sakata-Kato T, Jiang X, Kato N, Yan N, Yin H Proc Natl Acad Sci U S A. 2021 Jan 19;118(3). pii: 2017749118. doi:, 10.1073/pnas.2017749118. PMID:33402433 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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