BBMB Research Seminars

Thursday, August 31
Dr. Joseph Krzycki
Dept. of Microbiology
Ohio State University
"Genetically encoded pyrrolysine: why and how to send the message, and the importance of prepping the messenger"
1414 Molecular Biology Buidling
4:10 p.m.

Pyrrolysine is the 22nd genetically encoded amino acid to be found in nature. UAG codons within transcripts encoding methylamine methyltransferases are translated as pyrrolysine in certain methane forming Archaea. Pyrrolysine is found in an active site cleft within MtmB1, a monomethylamine methyltransferase. Mutagenic and inhibitor studies support pyrrolysine as having a catalytic role in methyltransferase function. A UAG-decoding tRNAPyl is dedicated to pyrrolysine. Deletion of tRNAPyl renders methanogens unable to use methylamines, but not other substrates, suggesting that pyrrolysine was recruited to the genetic code of these methanogens specifically for methylamine metabolism. The genetic encoding of pyrrolysine was anticipated to be most like that of selenocysteine, the only known example of a genetically encoded non-canonical amino acid. Selenocysteine is not a free amino acid, but is synthesized upon its tRNA. Against expectation, pyrrolysine is made as a free amino acid and charged directly onto tRNAPyl by a dedicated pyrrolysyl-tRNA synthetase. This is the first aminoacyl-tRNA synthetase found in nature that is specific for a non-canonical amino acid. Cis-acting elements within selenoprotein transcripts allow UGA to be translated as selenocysteine. We have investigated the context required for UAG translation as pyrrolysine, and have found it has both commonality and dissimilarity with selenocysteine. It now appears that the 22nd amino acid does have some similarities to selenocysteine, but the genetic encoding of pyrrolysine overall is more analogous to the common set of twenty amino acids.