1obs
|
STRUCTURE OF RICIN A CHAIN MUTANT
OverviewOverview
The A chain of ricin (RTA) is an N-glycosidase which inactivates ribosomes, by removing a single adenine base from a conserved region of rRNA. X-ray, structures and site-directed mutagenesis revealed that Arg 180 interacts, with the target adenine hydrogen bonding with N3. It may fully or, partially protonate that atom as part of the hydrolysis mechanism. Arg 180, was previously converted to His (R180H) and shown to greatly reduce, activity. Here R180H is shown to reduce overall activity 500-fold against, Artemia salina ribosomes. A 2.2 A crystal structure reveals the mutation, causes a rearrangement of the active site cleft, with Tyr 80 moving to, block access to the adenine recognition site. His 180 forms a strong, aromatic interaction with Trp 211, Tyr 80, and Tyr 123. A complex is, formed with 250 mM AMP. The nucleotide binds in the active site region, but in an apparently nonproductive orientation. His 180 cannot bond to N3, and is screened from the substrate analog by the intervening Tyr 80. It, may be that natural polynucleotide substrates, using additional, interactions, can displace Tyr 80 and effect a productive binding.
About this StructureAbout this Structure
1OBS is a Single protein structure of sequence from Ricinus communis. Active as rRNA N-glycosylase, with EC number 3.2.2.22 Full crystallographic information is available from OCA.
ReferenceReference
Structure and activity of an active site substitution of ricin A chain., Day PJ, Ernst SR, Frankel AE, Monzingo AF, Pascal JM, Molina-Svinth MC, Robertus JD, Biochemistry. 1996 Aug 27;35(34):11098-103. PMID:8780513
Page seeded by OCA on Tue Nov 20 22:54:08 2007