4o3f

Crystal Structure of mouse PGK1 3PG and terazosin(TZN) ternary complex

spinqualitylabelsall models 4o3f, resolution 2.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4o3f is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3PG, TZN Related: 4o33 Activity: Phosphoglycerate kinase, with EC number 2.7.2.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed alpha1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis. Terazosin activates Pgk1 and Hsp90 to promote stress resistance.,Chen X, Zhao C, Li X, Wang T, Li Y, Cao C, Ding Y, Dong M, Finci L, Wang JH, Li X, Liu L Nat Chem Biol. 2014 Nov 10. doi: 10.1038/nchembio.1657. PMID:25383758 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoglycerate Kinase

Proteopedia Page Contributors and Editors (what is this?)

OCA