6HTM

X-ray structure of the tryptophan lyase NosL in complex with bound tryptamin

Summary for 6HTM

• Entry DOI: 10.2210/pdb6htm/pdb
• Related: 6HTK
• Descriptor: 3-methyl-2-indolic acid synthase, 2-(1H-INDOL-3-YL)ETHANAMINE, IRON/SULFUR CLUSTER, ... (10 entities in total)
• Functional Keywords: radical sam, tryptophan lyase, nosiheptide, antibiotic
• Biological source: Streptomyces actuosus
• Total number of polymer chains: 2
• Total formula weight: 92423.75

Authors

Amara, P.,Mouesca, J.M.,Bella, M.,Saragaglia, C.,Gambarelli, S.,Nicolet, Y. (deposition date: 2018-10-04, release date: 2018-11-21, Last modification date: 2024-01-24)

Primary citation

Amara, P.,Mouesca, J.M.,Bella, M.,Martin, L.,Saragaglia, C.,Gambarelli, S.,Nicolet, Y.
Radical S-Adenosyl-l-methionine Tryptophan Lyase (NosL): How the Protein Controls the Carboxyl Radical •CO2-Migration.
J.Am.Chem.Soc., 140:16661-16668, 2018

PubMed Abstract: The radical S-adenosyl-l-methionine tryptophan lyase uses radical-based chemistry to convert l-tryptophan into 3-methyl-2-indolic acid, a fragment in the biosynthesis of the thiopeptide antibiotic nosiheptide. This complex reaction involves several successive steps corresponding to (i) the activation by a specific hydrogen-atom abstraction, (ii) an unprecedented •CO radical migration, (iii) a cyanide fragment release, and (iv) the termination of the radical-based reaction. In vitro study of this reaction is made more difficult because the enzyme produces a significant amount of a shunt product instead of the natural product. Here, using a combination of X-ray crystallography, electron paramagnetic resonance spectroscopy, and quantum and hybrid quantum mechanical/molecular mechanical calculations, we have deciphered the fine mechanism of the key •CO radical migration, highlighting how the preorganized active site of the protein tightly controls this reaction.

PubMed: 30418774
DOI: 10.1021/jacs.8b09142

Experimental method

X-RAY DIFFRACTION (1.7 Å)