3hh7

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)

spinqualitylabelsall models 3hh7, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hh7 is a 2 chain structure with sequence from Ophiophagus hannah. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 3SO8_OPHHA Antagonist of muscle (alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE) and neuronal (alpha-7/CHRNA7, alpha-3-beta-2/CHRNA3-CHRNB2, alpha-4-beta-2/CHRNA4-CHRNB2) nicotinic acetylcholine receptors (nAChR) (PubMed:20071329). The highest affinity is for human alpha-7/CHRNA7 nAChRs (IC(50)=180 nM), compared to human alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE nAChR (IC(50)= 550 nM), alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (IC(50)=500 nM), and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR (IC(50)=2.6 uM). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs. Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (king cobra).,Roy A, Zhou X, Chong MZ, D'hoedt D, Foo CS, Rajagopalan N, Nirthanan S, Bertrand D, Sivaraman J, Kini RM J Biol Chem. 2010 Mar 12;285(11):8302-15. Epub 2010 Jan 13. PMID:20071329 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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