1DEY

NMR SOLUTION STRUCTURE OF CO(II)-BLEOMYCIN A2

Summary for 1DEY

• Entry DOI: 10.2210/pdb1dey/pdb
• NMR Information: BMRB: 4667
• Descriptor: BLEOMYCIN A2, COBALT (II) ION (2 entities in total)
• Functional Keywords: antibiotic
• Total formula weight: 1475.49

Authors

Lehmann, T.E.,Serrano, M.L.,Que Jr., L. (deposition date: 1999-11-16, release date: 2000-04-24, Last modification date: 2024-05-22)

Primary citation

Lehmann, T.E.,Serrano, M.L.,Que Jr., L.
Coordination chemistry of co(II)-bleomycin: its investigation through NMR and molecular dynamics.
Biochemistry, 39:3886-3898, 2000

PubMed Abstract: Previous studies on the coordination chemistry of Co-bleomycin have suggested the secondary amine in beta-aminoalanine, the N5 and N1 nitrogens in the pyrimidine and imidazole rings, respectively, and the amide nitrogen in beta-hydroxyhistidine as equatorial ligands to the cobalt ion. The primary amine in beta-aminoalanine and the carbamoyl group of the mannose have been proposed alternatively as possible axial ligands. The first coordination sphere of Co(II) in Co(II)BLM has been investigated in the present study through the use of NMR and molecular dynamics calculations. The data collected from the NMR experiments are in agreement with the equatorial ligands previously proposed, and also support the participation of the primary amine as an axial ligand. The paramagnetic shifts of the gulose and mannose protons could suggest the latter as a second axial ligand. This possibility was investigated by way of molecular dynamics, with distance restraints derived from the relaxation times measured through NMR. The molecular dynamics results indicate that the most favorable structure is six-coordinate, with the primary amine and either the carbamoyl oxygen or a solvent molecule occupying the axial sites. The analysis of the structures previously derived for HOO-Co(III)-bleomycin and HOO-Co(III)-pepleomycin led us to propose the six-coordinate structure with only endogenous ligands, as the one held in solution by the Co(II) derivative of bleomycin.

PubMed: 10747776
DOI: 10.1021/bi991841p

Experimental method

SOLUTION NMR