1AO2

cobalt(III)-deglycopepleomycin determined by NMR studies

Summary for 1AO2

• Entry DOI: 10.2210/pdb1ao2/pdb
• Descriptor: AGLYCON OF PEPLOMYCIN, COBALT (III) ION, HYDROGEN PEROXIDE (3 entities in total)
• Functional Keywords: anticancer drugs, deglycosylated pepleomycin, peplomycin, bleomycin, dna, two-dimensional nmr, solution structures, inhibitor
• Total formula weight: 1199.23

Authors

Caceres-Cortes, J.,Sugiyama, H.,Ikudome, K.,Saito, I.,Wang, A.H.-J. (deposition date: 1997-07-16, release date: 1999-07-30, Last modification date: 2024-03-13)

Primary citation

Caceres-Cortes, J.,Sugiyama, H.,Ikudome, K.,Saito, I.,Wang, A.H.
Structures of cobalt(III)-pepleomycin and cobalt(III)-deglycopepleomycin (green forms) determined by NMR studies.
Eur.J.Biochem., 244:818-828, 1997

PubMed Abstract: Pepleomycin (PEP) is a metalloglycopeptide that has stronger anticancer activity and less pulmonary toxicity than bleomycin (BLM). PEP, like BLM, exerts its action by binding to and degrading DNA in the presence of oxygen and certain metals. Obtaining detailed structural information of PEP and PEP-DNA complexes is crucial to understanding its anticancer activity. The structures of two green forms of cobalt-PEP species, HO2-Co(III)-PEP (denoted CoPEP) and deglycosylated HO2-Co(III)-PEP (denoted CodPEP) have been obtained by NOE restrained refinements. Earlier studies of the related HO2-Co(III)-BLM A2 proposed that two chiral conformers (form A or B) could exist with either the beta-aminoalanine primary amine (A,NH2) or the mannose carbamoyl nitrogen (M,NH2) as the axial ligand. Analysis of our NOESY data shows convincingly that form A is the most probable conformer with the mannose carbamoyl M,NH2 and the beta-aminoalanine primary amine A,NH2 as the axial ligands in CoPEP and CodPEP, respectively. The NOE cross-peaks resulting from the interactions between the N-terminus (i.e., the metal-binding domain) and the C-terminus of CoPEP and CodPEP have similar patterns, suggesting that they both adopt compact structures with the bithiazole group folded back over the N-terminus.

PubMed: 9108252
DOI: 10.1111/j.1432-1033.1997.00818.x

Experimental method

SOLUTION NMR