4bds

Human butyrylcholinesterase in complex with tacrine

spinqualitylabelsall models 4bds, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bds 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 2.1Å Ligands: CL, FPK, FUC, FUL, GOL, NAG, SO4, THA, UNX Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CHLE_HUMAN Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:177400. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait. Function CHLE_HUMAN Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters. Publication Abstract from PubMed The multifunctional nature of Alzheimer's disease calls for multi-target directed ligands (MTDLs) able to act on different components of the pathology, like the cholinergic dysfunction and amyloid aggregation. Such MTDLs are usually based on cholinesterase inhibitors (e.g., tacrine or huprine) coupled to another active molecule aimed at a different target. To aid in the design of these MTDLs we report the crystal structures of human acetylcholinesterase (hAChE) in complex with FAS-2 and a hydroxylated derivative of huprine (huprine W), and of human butyrylcholinesterase (hBChE) in complex with tacrine. Huprine W in hAChE and tacrine in hBChE reside in strikingly similar positions highlighting the conservation of key interactions, namely, pi-pi/cation-pi interactions with Trp86(82), and hydrogen bonding with the main chain carbonyl of the catalytic histidine. Huprine W forms additional interactions with hAChE which explains its superior affinity: the isoquinoline moiety is associated with a group of aromatic residues (Tyr337, Phe338 and Phe295 not present in hBChE) in addition to Trp86; the hydroxyl group is hydrogen bonded to both the catalytic serine and residues in the oxyanion hole; and the chlorine substituent is nested in a hydrophobic pocket interacting strongly with Trp439. There is no pocket in hBChE able to accommodate the chlorine substituent. Crystal Structures of Human Cholinesterases in Complex with Huprine W and Tacrine: Elements of Specificity for Anti-Alzheimer's Drugs Targeting Acetyl- and Butyrylcholinesterase.,Nachon F, Carletti E, Ronco C, Trovaslet M, Nicolet Y, Jean L, Renard PY Biochem J. 2013 May 17. PMID:23679855 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Butyrylcholinesterase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA