Structural highlights
Function
[NCZS_STRCZ] NCS has antibiotic activity (for Gram-positive bacteria) and antitumor activity (for certain mouse tumors). NCS binds non-covalently to a chromophore which is the cytotoxic and mutagenic component of the antibiotic. The chromophore binds to DNA as a weak intercalator and causes single- and double-strand breaks.
Publication Abstract from PubMed
Neocarzinostatin (NCS) is a 1:1 complex of an enediyne chromophore (NCSChrom), non-covalently bound to an 11 kDa protein (apoNCS). We are exploring apoNCS as a generic protein system for sequestering small molecules for therapeutic applications. Here, we disclose a new flavone ligand 1 for apoNCS and present a high-resolution NMR structure of this ligand bound to apoNCS. This is the first high-resolution structure of a completely non-cognate ligand bound to the apoNCS protein. This work provides unambiguous evidence that a completely new class of ligand can bind specifically to apoNCS. Furthermore, the mode of binding is different than that of the naphthoate-based ligands, and for such a simple hydrophobic compound, the new ligand surprisingly binds specifically. This work indicates that apo-Neocarzinostatin has multiple selective and distinct binding modes for small-molecule cargo.
Synthetic ligands for apo-neocarzinostatin.,Caddick S, Muskett FW, Stoneman RG, Woolfson DN J Am Chem Soc. 2006 Apr 5;128(13):4204-5. PMID:16568976[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Caddick S, Muskett FW, Stoneman RG, Woolfson DN. Synthetic ligands for apo-neocarzinostatin. J Am Chem Soc. 2006 Apr 5;128(13):4204-5. PMID:16568976 doi:10.1021/ja058419i
