Editing Methionine (section)

==A proteinogenic amino acid==
[[Cysteine]] and methionine are the two [[sulfur]]-containing [[proteinogenic amino acid]]s. Excluding the few exceptions where methionine may act as a [[redox sensor]] (e.g.,[[methionine sulfoxide]]<ref>{{Cite journal |vauthors=Bigelow DJ, Squier TC |date=January 2005 |title=Redox modulation of cellular signaling and metabolism through reversible oxidation of methionine sensors in calcium regulatory proteins |journal=Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |url=https://zenodo.org/record/1258778 |type=Submitted manuscript |volume=1703 |issue=2 |pages=121–134 |doi=10.1016/j.bbapap.2004.09.012 |pmid=15680220}}</ref>), methionine residues do not have a catalytic role.<ref name="review">{{Cite journal |vauthors=Ferla MP, Patrick WM |date=August 2014 |title=Bacterial methionine biosynthesis |journal=Microbiology |volume=160 |issue=Pt 8 |pages=1571–1584 |doi=10.1099/mic.0.077826-0 |pmid=24939187|doi-access=free }}</ref> This is in contrast to cysteine residues, where the thiol group has a catalytic role in many proteins.<ref name=review/> The thioether within methionine does however have a minor structural role due to the stability effect of [[S/π interaction]]s between the side chain sulfur atom and aromatic amino acids in one-third of all known protein structures.<ref name=review/> This lack of a strong role is reflected in experiments where little effect is seen in proteins where methionine is replaced by [[norleucine]], a straight hydrocarbon sidechain amino acid which lacks the thioether.<ref>{{Cite journal |vauthors=Cirino PC, Tang Y, Takahashi K, Tirrell DA, Arnold FH |date=September 2003 |title=Global incorporation of norleucine in place of methionine in cytochrome P450 BM-3 heme domain increases peroxygenase activity |journal=Biotechnology and Bioengineering |volume=83 |issue=6 |pages=729–734 |doi=10.1002/bit.10718 |pmid=12889037|s2cid=11380413 }}</ref>
It has been conjectured that norleucine was present in early versions of the genetic code, but methionine intruded into the final version of the genetic code due to the fact it is used in the cofactor [[S-adenosylmethionine|''S''-adenosylmethionine]] (SAM-e).<ref>{{Cite journal |vauthors=Alvarez-Carreño C, Becerra A, Lazcano A |date=October 2013 |title=Norvaline and norleucine may have been more abundant protein components during early stages of cell evolution |journal=Origins of Life and Evolution of the Biosphere |volume=43 |issue=4–5 |pages=363–375 |bibcode=2013OLEB...43..363A |doi=10.1007/s11084-013-9344-3 |pmid=24013929|s2cid=17224537 }}</ref> This situation is not unique and may have occurred with [[ornithine]] and [[arginine]].<ref>{{Cite journal |vauthors=Jukes TH |date=August 1973 |title=Arginine as an evolutionary intruder into protein synthesis |journal=Biochemical and Biophysical Research Communications |volume=53 |issue=3 |pages=709–714 |doi=10.1016/0006-291x(73)90151-4 |pmid=4731949}}</ref>

===Encoding===
Methionine is one of only two amino acids encoded by a single [[codon]] (AUG) in the standard [[genetic code]] ([[tryptophan]], encoded by UGG, is the other). In reflection to the evolutionary origin of its codon, the other AUN codons encode [[isoleucine]], which is also a hydrophobic amino acid. In the mitochondrial genome of several organisms, including [[Vertebrate mitochondrial code|metazoa]] and [[The yeast mitochondrial code|yeast]], the codon AUA also encodes for methionine. In the standard genetic code AUA codes for isoleucine and the respective tRNA (''ileX'' in ''Escherichia coli'') uses the unusual base [[Lysidine (nucleoside)|lysidine]] (bacteria) or [[agmatidine]] (archaea) to discriminate against AUG.<ref>{{Cite journal |vauthors=Ikeuchi Y, Kimura S, Numata T, Nakamura D, Yokogawa T, Ogata T, Wada T, Suzuki T, Suzuki T |date=April 2010 |title=Agmatine-conjugated cytidine in a tRNA anticodon is essential for AUA decoding in archaea |journal=Nature Chemical Biology |volume=6 |issue=4 |pages=277–282 |doi=10.1038/nchembio.323 |pmid=20139989}}</ref><ref>{{Cite journal |vauthors=Muramatsu T, Nishikawa K, Nemoto F, Kuchino Y, Nishimura S, Miyazawa T, Yokoyama S |date=November 1988 |title=Codon and amino-acid specificities of a transfer RNA are both converted by a single post-transcriptional modification |journal=Nature |volume=336 |issue=6195 |pages=179–181 |bibcode=1988Natur.336..179M |doi=10.1038/336179a0 |pmid=3054566|s2cid=4371485 }}</ref>

The methionine codon AUG is also the most common start codon. A "Start" codon is message for a [[ribosome]] that signals the initiation of protein [[Translation (biology)|translation]] from mRNA when the AUG codon is in a [[Kozak consensus sequence]]. As a consequence, methionine is often incorporated into the ''N''-terminal position of [[protein]]s in [[eukaryote]]s and [[archaea]] during translation, although it can be removed by [[post-translational modification]]. In [[bacteria]], the derivative [[N-Formylmethionine|''N''-formylmethionine]] is used as the initial amino acid.{{cn|date=October 2024}}