1s5c: Difference between revisions

|PDB= 1s5c |SIZE=350|CAPTION= <scene name='initialview01'>1s5c</scene>, resolution 2.50&Aring;

|SITE=  

|LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>

|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] </span>

|GENE= CTXA, TOXA, VC1457 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 Vibrio cholerae]), CTXB, TOXB, VC1456 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 Vibrio cholerae])

|RELATEDENTRY=[[1xtc|1XTC]], [[1lts|1LTS]], [[1ltg|1LTG]], [[1lta|1LTA]]

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s5c OCA], [http://www.ebi.ac.uk/pdbsum/1s5c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s5c RCSB]</span>

'''Cholera holotoxin with an A-subunit Y30S mutation, Crystal form 1'''

==Overview==

Cholera toxin (CT) is a heterohexameric bacterial protein toxin belonging to a larger family of A/B ADP-ribosylating toxins. Each of these toxins undergoes limited proteolysis and/or disulfide bond reduction to form the enzymatically active toxic fragment. Nicking and reduction render both CT and the closely related heat-labile enterotoxin from Escherichia coli (LT) unstable in solution, thus far preventing a full structural understanding of the conformational changes resulting from toxin activation. We present the first structural glimpse of an active CT in structures from three crystal forms of a single-site A-subunit CT variant, Y30S, which requires no activational modifications for full activity. We also redetermined the structure of the wild-type, proenzyme CT from two crystal forms, both of which exhibit (i) better geometry and (ii) a different A2 "tail" conformation than the previously determined structure [Zhang et al. (1995) J. Mol. Biol. 251, 563-573]. Differences between wild-type CT and active CTY30S are observed in A-subunit loop regions that had been previously implicated in activation by analysis of the structure of an LT A-subunit R7K variant [van den Akker et al. (1995) Biochemistry 34, 10996-11004]. The 25-36 activation loop is disordered in CTY30S, while the 47-56 active site loop displays varying degrees of order in the three CTY30S structures, suggesting that disorder in the activation loop predisposes the active site loop to a greater degree of flexibility than that found in unactivated wild-type CT. On the basis of these six new views of the CT holotoxin, we propose a model for how the activational modifications experienced by wild-type CT are communicated to the active site.

 

1S5C is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5C OCA].

 

==Reference==

Crystal structures of an intrinsically active cholera toxin mutant yield insight into the toxin activation mechanism., O'Neal CJ, Amaya EI, Jobling MG, Holmes RK, Hol WG, Biochemistry. 2004 Apr 6;43(13):3772-82. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15049684 15049684]

[[Category: Protein complex]]

[[Category: Amaya, E I.]]

[[Category: Hol, W G.]]

[[Category: Holmes, R K.]]

[[Category: Jobling, M G.]]

[[Category: Neal, C J.O.]]

[[Category: cholera toxin]]