View source for 1giq

[[Image:1giq.jpg|left|200px]]<br /><applet load="1giq" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1giq, resolution 1.80&Aring;" />
'''CRYSTAL STRUCTURE OF THE ENZYMATIC COMPONET OF IOTA-TOXIN FROM CLOSTRIDIUM PERFRINGENS WITH NADH'''<br />

==Overview==
Iota-toxin from Clostridium perfringens type E is an ADP-ribosylating, toxin (ADPRT) that ADP-ribosylates actin, which is lethal and, dermonecrotic in mammals. It is a binary toxin composed of an enzymatic, component (Ia) and a binding component (Ib). Ia ADP-ribosylates G-actin at, arginine 177, resulting in the depolymerization of the actin cytoskeleton., Here, we report on studies of the structure-function relationship by the, crystal structures of Ia complexed with NADH and NADPH (at 1.8 A and 2.1 A, resolution, respectively) and mutagenesis that map the active residues., The catalytic C-domain structure was similar to that of Bacillus cereus, vegetative insecticidal protein (VIP2), which is an insect-targeted toxin, except for the EXE loop region. However, a significant structural, difference could be seen in the N-domain, which interacts with Ib, suggesting an evolutionary difference between mammalian-targeted and, insect-targeted ADPRT. The high resolution structure analysis revealed, specific NAD conformation (a ring-like conformation of nicotinamide, mononucleotide (NMN)) supported by Arg295, Arg296, Asn335, Arg352 and, Glu380. Additionally, the mutagenesis study showed that the residues, Tyr251, Arg295, Glu301, Ser338, Phe349, Arg352 and Glu380, including a, newly identified one, are essential for NAD(+)-glycohydrolase (NADase), activity. At least one residue, Glu378, is an essential residue for, ADP-ribosyltransferase (ARTase), but not for NADase. Consequently, the, structural feature and these mutagenesis findings suggest that the, catalytic mechanism of Ia proceeds via an Sn1-type reaction.

==About this Structure==
1GIQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens] with NAD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GIQ OCA]. 

==Reference==
Crystal structure and site-directed mutagenesis of enzymatic components from Clostridium perfringens iota-toxin., Tsuge H, Nagahama M, Nishimura H, Hisatsune J, Sakaguchi Y, Itogawa Y, Katunuma N, Sakurai J, J Mol Biol. 2003 Jan 17;325(3):471-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12498797 12498797]
[[Category: Clostridium perfringens]]
[[Category: Single protein]]
[[Category: Hisatsune, J.]]
[[Category: Itogawa, Y.]]
[[Category: Katunuma, N.]]
[[Category: Nagahama, M.]]
[[Category: Nishimura, H.]]
[[Category: Sakaguchi, Y.]]
[[Category: Sakurai, J.]]
[[Category: Tsuge, H.]]
[[Category: NAD]]
[[Category: enzymatic component]]

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