1hzk

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1hzk

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SOLUTION STRUCTURES OF C-1027 APOPROTEIN AND ITS COMPLEX WITH THE AROMATIZED CHROMOPHORE

Overview

C-1027 is one of the most potent antitumor antibiotic chromoproteins, and, is a 1:1 complex of an enediyne chromophore having DNA-cleaving ability, and a carrier apoprotein. The three-dimensional solution structures of the, 110 residue (10.5 kDa) C-1027 apoprotein and its complex with the, aromatized chromophore have been determined separately by homonuclear, two-dimensional nuclear magnetic resonance methods. The apoprotein is, mainly composed of three antiparallel beta-sheets: four-stranded, beta-sheet (43-45, 52-54; 30-38; 92-94; 104-106), three-stranded, beta-sheet (4-6; 17-22; 61-66), and two-stranded beta-sheet (70-72;, 83-85). The overall structure of the apoprotein is very similar to those, of other chromoprotein apoproteins, such as neocarzinostatin and, kedarcidin. A hydrophobic pocket with approximate dimensions of 14 A x 12, A x 8 A is formed by the four-stranded beta-sheet and the three loops, (39-42; 75-79; 97-100). The holoprotein (complex form with the aromatized, chromophore) structure reveals that the aromatized chromophore is bound to, the hydrophobic pocket found in the apoprotein. The benzodihydropentalene, core of the chromophore is located in the center of the pocket and other, substituents (beta-tyrosine, benzoxazine, and aminosugar moieties) are, arranged around the core. Major binding interactions between the, apoprotein and the chromophore are likely the hydrophobic contacts between, the core of the chromophore and the hydrophobic side-chains of the, pocket-forming residues, which is supplemented by salt bridges and/or, hydrogen bonds. Based on the holoprotein structure, we propose possible, mechanisms for the stabilization and the release of chromophore by the, apoprotein.

About this Structure

1HZK is a Single protein structure of sequence from Streptomyces globisporus. Full crystallographic information is available from OCA.

Reference

Solution structures of C-1027 apoprotein and its complex with the aromatized chromophore., Tanaka T, Fukuda-Ishisaka S, Hirama M, Otani T, J Mol Biol. 2001 May 25;309(1):267-83. PMID:11491295

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