Solution structure of a novel chromoprotein derived from apo-neocarzinostatin and a synthetic chromophore.
The natural complex Neocarzinostatin comprises a labile chromophore noncovalently bound to an 11.2 kDa protein. We present the first high-resolution structure of a novel complex derived from the recombinant apoprotein bound to a non-natural synthetic chromophore. Fluorescence and nuclear magnetic resonance spectroscopy were used to probe the strength and location of binding. Binding occurred in a location similar to that observed for the chromophore in the natural Neocarzinostatin complex, but with a distinct orientation. These results provide structural evidence that the apoprotein can readily accommodate small druglike entities, other than the natural chromophore within its binding cleft. The clinical use of the natural complex described by others, together with the results reported here, suggests potential applications for small molecule binding by apo-Neocarzinostatin.
Urbaniak
Michael D
MD
Centre for Biomolecular Design and Drug Development, CPES, University of Sussex, Falmer, Lewes Road, Brighton BN1 9QJ, U.K.
Muskett
Frederick W
FW
Finucane
Michael D
MD
Caddick
Stephen
S
Woolfson
Derek N
DN
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification; D001059:Apoproteins / Q000737:chemistry* / Q000302:isolation & purification; D001665:Binding Sites; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D053281:Enediynes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification; D012996:Solutions; D013050:Spectrometry, Fluorescence; D009353:Zinostatin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000302:isolation & purification
D000903:Antibiotics, Antineoplastic; D001059:Apoproteins; D053281:Enediynes; D011993:Recombinant Fusion Proteins; D012996:Solutions; C032372:neocarzinostatin chromophore; D009353:Zinostatin