4R33

X-ray structure of the tryptophan lyase NosL with Tryptophan and S-adenosyl-L-homocysteine bound

Summary for 4R33

• Entry DOI: 10.2210/pdb4r33/pdb
• Related: 4R34
• Descriptor: NosL, S-ADENOSYL-L-HOMOCYSTEINE, IRON/SULFUR CLUSTER, ... (9 entities in total)
• Functional Keywords: radical sam enzyme/beta-alpha barrel, tryptophan lyase, fe4s4 cluster and s-adenosyl-l-methionine, lyase
• Biological source: Streptomyces actuosus
• Total number of polymer chains: 2
• Total formula weight: 96088.20

Authors

Nicolet, Y.,Zeppieri, L.,Amara, P.,Fontecilla-Camps, J.-C. (deposition date: 2014-08-14, release date: 2014-09-17, Last modification date: 2024-02-28)

Primary citation

Nicolet, Y.,Zeppieri, L.,Amara, P.,Fontecilla-Camps, J.C.
Crystal Structure of Tryptophan Lyase (NosL): Evidence for Radical Formation at the Amino Group of Tryptophan.
Angew.Chem.Int.Ed.Engl., 53:11840-11844, 2014

PubMed Abstract: Streptomyces actuosus tryptophan lyase (NosL) is a radical SAM enzyme which catalyzes the synthesis of 3-methyl-2-indolic acid, a precursor in the synthesis of the promising antibiotic nosiheptide. The reaction involves cleavage of the tryptophan Cα-Cβ bond and recombination of the amino-acid-derived -COOH fragment at the indole ring. Reported herein is the 1.8 Å resolution crystal structure of NosL complexed with its substrate. Unexpectedly, only one of the tryptophan amino hydrogen atoms is optimally placed for H abstraction by the SAM-derived 5'-deoxyadenosyl radical. This orientation, in turn, rules out the previously proposed delocalized indole radical as the species which undergoes Cα-Cβ bond cleavage. Instead, stereochemical considerations indicate that the reactive intermediate is a (·)NH tryptophanyl radical. A structure-based amino acid sequence comparison of NosL with the tyrosine lyases ThiH and HydG strongly suggests that an equivalent (·)NH radical operates in the latter enzymes.

PubMed: 25196319
DOI: 10.1002/anie.201407320

Experimental method

X-RAY DIFFRACTION (1.78 Å)