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Crystal structure of the tet repressor in complex with a novel tetracycline, 9-(N,N-dimethylglycylamido)- 6-demethyl-6-deoxy-tetracycline.

Abstract：

:The tetracycline analog 9-(N, N-dimethylglycylamido)-6-demethyl-6-deoxy-tetracycline (9glyTc) belongs to a new group of tetracyclines called glycylcyclines. They are strong antibiotics showing reduced sensitivity against the major tetracycline resistance mechanisms. We have determined the crystal structure of 9glyTc in complex with Tet repressor class D, TetR(D), at 2.4 A resolution. Sterical hindrance at the entrance of the tetracycline binding tunnel of TetR by the bulky and charged glycyl amido substituent interferes with conformational changes required for the mechanism of induction, and leads to decreased induction efficiency as observed for point mutations of amino acid residues located in the neighbourhood to the glycylamido moiety of bound 9glyTc.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Orth P,Schnappinger D,Sum PE,Ellestad GA,Hillen W,Saenger W,Hinrichs W

doi

10.1006/jmbi.1998.2290

subject

Has Abstract

pub_date

1999-01-15 00:00:00

pages

455-61

issue

2

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(98)92290-2

journal_volume

285

pub_type

杂志文章

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