1ao4
From Proteopedia
(New page: 200px<br /><applet load="1ao4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ao4" /> '''COBALT(III)-PEPLOMYCIN COMPLEX DETERMINED BY...) |
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| - | [[Image:1ao4.gif|left|200px]]<br /><applet load="1ao4" size=" | + | [[Image:1ao4.gif|left|200px]]<br /><applet load="1ao4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ao4" /> | caption="1ao4" /> | ||
'''COBALT(III)-PEPLOMYCIN COMPLEX DETERMINED BY NMR STUDIES'''<br /> | '''COBALT(III)-PEPLOMYCIN COMPLEX DETERMINED BY NMR STUDIES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pepleomycin (PEP) is a metalloglycopeptide that has stronger anticancer | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1AO4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with 3CO, PMY and PEO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1AO4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=3CO:'>3CO</scene>, <scene name='pdbligand=PMY:'>PMY</scene> and <scene name='pdbligand=PEO:'>PEO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saito, I.]] | [[Category: Saito, I.]] | ||
[[Category: Sugiyama, H.]] | [[Category: Sugiyama, H.]] | ||
| - | [[Category: Wang, A | + | [[Category: Wang, A H.J.]] |
[[Category: 3CO]] | [[Category: 3CO]] | ||
[[Category: PEO]] | [[Category: PEO]] | ||
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[[Category: two-dimensional nmr]] | [[Category: two-dimensional nmr]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:46:31 2008'' |
Revision as of 09:46, 21 February 2008
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COBALT(III)-PEPLOMYCIN COMPLEX DETERMINED BY NMR STUDIES
Overview
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.
About this Structure
1AO4 is a Protein complex structure of sequences from [1] with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structures of cobalt(III)-pepleomycin and cobalt(III)-deglycopepleomycin (green forms) determined by NMR studies., Caceres-Cortes J, Sugiyama H, Ikudome K, Saito I, Wang AH, Eur J Biochem. 1997 Mar 15;244(3):818-28. PMID:9108252
Page seeded by OCA on Thu Feb 21 11:46:31 2008
Categories: Protein complex | Caceres-Cortes, J. | Ikudome, K. | Saito, I. | Sugiyama, H. | Wang, A H.J. | 3CO | PEO | PMY | Anticancer drugs | Bleomycin | Dna | Pepleomycin | Peplomycin | Solution structures | Two-dimensional nmr
