In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 11 ( 2001-05-22), p. 6021-6026
Abstract:
The crystal structure of anthranilate synthase (AS) from Serratia marcescens, a mesophilic bacterium, has been
solved in the presence of its substrates, chorismate and glutamine, and one product, glutamate, at 1.95 Å, and with its bound feedback
inhibitor, tryptophan, at 2.4 Å. In comparison with the AS structure from the hyperthermophile Sulfolobus solfataricus , the S. marcescens structure shows similar subunit structures
but a markedly different oligomeric organization. One crystal form of the S. marcescens enzyme displays a bound pyruvate as
well as a putative anthranilate (the nitrogen group is ambiguous) in the TrpE subunit. It also confirms the presence of a covalently bound
glutamyl thioester intermediate in the TrpG subunit. The tryptophan-bound form reveals that the inhibitor binds at a site
distinct from that of the substrate, chorismate. Bound tryptophan appears to prevent chorismate binding by a demonstrable conformational
effect, and the structure reveals how occupancy of only one of the two feedback inhibition sites can immobilize the catalytic activity of both
TrpE subunits. The presence of effectors in the structure provides a view of the locations of some of the amino acid residues in the active
sites. Our findings are discussed in terms of the previously described AS structure of S. solfataricus , mutational data
obtained from enteric bacteria, and the enzyme's mechanism of action.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.111150298
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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