Structural insight into the self-sacrifice mechanism of enediyne resistance.

Structural insight into the self-sacrifice mechanism of enediyne resistance. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Structural insight into the self-sacrifice mechanism of enediyne resistance. Abstract Text:

Shanteri Singh,Martin H Hager,Changsheng Zhang,Byron R Griffith,Min S Lee,Klaas Hallenga,John L Markley,Jon S Thorson,

The recent discovery of the first "self-sacrifice" mechanism for bacterial resistance to the enediyne antitumor antibiotics, where enediyne-induced proteolysis of the resistance protein CalC inactivates both the highly reactive metabolite and the resistance protein, revealed yet another ingenious bacterial mechanism for controlling reactive metabolites. As reported herein, the first 3D structures of CalC and CalC in complex with calicheamicin (CLM) divulge CalC to be a member of the steroidogenic acute regulatory protein (StAR)-related transfer (START) domain superfamily. In contrast to previous studies of proteins known to bind DNA-damaging natural products ( e.g ., bleomycins, mitomycins, and nine-membered chromoprotein enediynes), this is the first demonstrated involvement of a START domain fold. Consistent with the CalC self-sacrifice mechanism, CLM in complex with CalC is positioned for direct hydrogen abstraction from Gly113 to initiate the oxidative proteolysis-based resistance mechanism. These structural studies also illuminate, for the first time, a small DNA-binding region within CalC that may serve to localize CalC to the enediyne target (DNA). Given the role of START domains in nuclear/cytosolic transport and translocation, this structural study also may implicate START domains as post-endocytotic intracellular chaperones for enediyne-based therapeutics such as MyloTarg.

Structural insight into the self-sacrifice mechanism of enediyne resistance. Publishing Authors By Initials

S Singh,MH Hager,C Zhang,BR Griffith,MS Lee,K Hallenga,JL Markley,JS Thorson,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: biological transport: protein transport research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: biological transport: protein transport research

PUBMED ID PMID:

MEDLINE DATE:

Structural insight into the self-sacrifice mechanism of enediyne resistance. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: ACS chemical biology

VOLUME: 1

Page Numbers: 451-60

Journal Abbreviation: ACS Chem. Biol.

ISSN: 1554-8937

DAY: 22

MONTH: Aug

YEAR: 2006

Structural insight into the self-sacrifice mechanism of enediyne resistance. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101282906

Structural insight into the self-sacrifice mechanism of enediyne resistance. Keywords Mesh Terms:

KEYWORDS: Protein Transport

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Structural insight into the self-sacrifice mechanism of enediyne resistance. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Structural insight into the self-sacrifice mechanism of enediyne resistance.

AFFILIATION: Center for Eukaryotic Structural Genomics, Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706-1544, USA.

Country: United States

AGENCY: United States NCI

GRANT: U19 CA113297

ACRONYM: CA

MEDLINETA: ACS Chem Biol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Structural insight into the self-sacrifice mechanism of enediyne resistance Related Publications

• A comparison of sugar indicators enables a universal high-throughput sugar-1-phosphate nucleotidyltransferase assay.
• A high-throughput fluorescence-based glycosyltransferase screen and its application in directed evolution.
• Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis.
• Clinical implications of transplantability of induced bladder tumors to intact transitional epithelium in dogs.
• Colchicine glycorandomization influences cytotoxicity and mechanism of action.
• Enhancing the latent nucleotide triphosphate flexibility of the glucose-1-phosphate thymidylyltransferase RmlA.
• Expanding the promiscuity of a natural-product glycosyltransferase by directed evolution.
• Increasing carbohydrate diversity via amine oxidation: aminosugar, hydroxyaminosugar, nitrososugar, and nitrosugar biosynthesis in bacteria.
• Model for antibiotic optimization via neoglycosylation: synthesis of liponeoglycopeptides active against VRE.
• Needle aspiration biopsy in cystic papillary carcinoma of the thyroid.
• Society of trauma nurses position statement on the role of the clinical nurse specialist in trauma.
• Structural insight into the self-sacrifice mechanism of enediyne resistance.
• Structure and Mechanism of the Rebeccamycin Sugar 4'-O-Methyltransferase RebM.
• The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710.
• The in vitro characterization of polyene glycosyltransferases AmphDI and NysDI.
• The in vitro characterization of the erythronolide mycarosyltransferase EryBV and its utility in macrolide diversification.
• The in vitro characterization of the iterative avermectin glycosyltransferase AveBI reveals reaction reversibility and sugar nucleotide flexibility.