1g24
From Proteopedia
|
THE CRYSTAL STRUCTURE OF EXOENZYME C3 FROM CLOSTRIDIUM BOTULINUM
Overview
Clostridium botulinum C3 exoenzyme inactivates the small GTP-binding, protein family Rho by ADP-ribosylating asparagine 41, which depolymerizes, the actin cytoskeleton. C3 thus represents a major family of the bacterial, toxins that transfer the ADP-ribose moiety of NAD to specific amino acids, in acceptor proteins to modify key biological activities in eukaryotic, cells, including protein synthesis, differentiation, transformation, and, intracellular signaling. The 1.7 A resolution C3 exoenzyme structure, establishes the conserved features of the core NAD-binding beta-sandwich, fold with other ADP-ribosylating toxins despite little sequence, conservation. Importantly, the central core of the C3 exoenzyme structure, is distinguished by the absence of an active site loop observed in many, other ADP-ribosylating toxins. Unlike the ADP-ribosylating toxins that, possess the active site loop near the central core, the C3 exoenzyme, replaces the active site loop with an alpha-helix, alpha3. Moreover, structural and sequence similarities with the catalytic domain of, vegetative insecticidal protein 2 (VIP2), an actin ADP-ribosyltransferase, unexpectedly implicates two adjacent, protruding turns, which join beta5, and beta6 of the toxin core fold, as a novel recognition specificity motif, for this newly defined toxin family. Turn 1 evidently positions the, solvent-exposed, aromatic side-chain of Phe209 to interact with the, hydrophobic region of Rho adjacent to its GTP-binding site. Turn 2, evidently both places the Gln212 side-chain for hydrogen bonding to, recognize Rho Asn41 for nucleophilic attack on the anomeric carbon of NAD, ribose and holds the key Glu214 catalytic side-chain in the adjacent, catalytic pocket. This proposed bipartite ADP-ribosylating toxin turn-turn, (ARTT) motif places the VIP2 and C3 toxin classes into a single ARTT, family characterized by analogous target protein recognition via turn 1, aromatic and turn 2 hydrogen-bonding side-chain moieties. Turn 2 centrally, anchors the catalytic Glu214 within the ARTT motif, and furthermore, distinguishes the C3 toxin class by a conserved turn 2 Gln and the VIP2, binary toxin class by a conserved turn 2 Glu for appropriate target, side-chain hydrogen-bonding recognition. Taken together, these structural, results provide a molecular basis for understanding the coupled activity, and recognition specificity for C3 and for the newly defined ARTT toxin, family, which acts in the depolymerization of the actin cytoskeleton. This, beta5 to beta6 region of the toxin fold represents an experimentally, testable and potentially general recognition motif region for other, ADP-ribosylating toxins that have a similar beta-structure framework.
About this Structure
1G24 is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.
Reference
Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis., Han S, Arvai AS, Clancy SB, Tainer JA, J Mol Biol. 2001 Jan 5;305(1):95-107. PMID:11114250
Page seeded by OCA on Tue Nov 20 15:38:20 2007
