3fzy

Crystal Structure of Pre-cleavage Form of Cysteine Protease Domain from Vibrio cholerae RtxA Toxin

spinqualitylabelsall models 3fzy, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3fzy is a 2 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, IHP, UNX Related: 3eeb Gene: rtxA, VC_1451 ("Bacillo virgola del Koch" Trevisan 1884) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN 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 The multifunctional autoprocessing repeats-in-toxin (MARTX) toxin of Vibrio cholerae causes destruction of the actin cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases. The effector domains responsible for these activities are here shown to be independent proteins released from the large toxin by autoproteolysis catalyzed by an embedded cysteine protease domain (CPD). The CPD is activated upon binding inositol hexakisphosphate (InsP(6)). In this study, we demonstrated that InsP(6) is not simply an allosteric cofactor, but rather binding of InsP(6) stabilized the CPD structure, facilitating formation of the enzyme-substrate complex. The 1.95-A crystal structure of this InsP(6)-bound unprocessed form of CPD was determined and revealed the scissile bond Leu(3428)-Ala(3429) captured in the catalytic site. Upon processing at this site, CPD was converted to a form with 500-fold reduced affinity for InsP(6), but was reactivated for high affinity binding of InsP(6) by cooperative binding of both a new substrate and InsP(6). Reactivation of CPD allowed cleavage of the MARTX toxin at other sites, specifically at leucine residues between the effector domains. Processed CPD also cleaved other proteins in trans, including the leucine-rich protein YopM, demonstrating that it is a promiscuous leucine-specific protease. Structural and molecular mechanism for autoprocessing of MARTX toxin of Vibrio cholerae at multiple sites.,Prochazkova K, Shuvalova LA, Minasov G, Voburka Z, Anderson WF, Satchell KJ J Biol Chem. 2009 Sep 25;284(39):26557-68. Epub 2009 Jul 20. PMID:19620709 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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