Contributions of Zn(II)-binding to the structural stability of endostatin.
Endostatin has a compact structure with a Zn(II)-binding site (His1, His3, His11, and Asp76) at the N-terminus. In this study, the effects of Zn(II)-binding on the folding and stability of recombinant human endostatin were studied. The results show that Zn(II)-binding largely stabilizes the structure of endostatin at physiological pH. Under some proteolytic conditions, Zn(II)-binding also contributes to the integrity of the N-terminus of endostatin, which is critical for endostatin to maintain a stable structure. Moreover, engineering an extra Zn(II)-binding peptide to the N-terminus of human endostatin makes this molecule more stable and cooperative in the presence of Zn(II).
Han
Qing
Q
Laboratory of Protein Chemistry, the Protein Science Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, PR China.
Fu
Yan
Y
Zhou
Hao
H
He
Yingbo
Y
Luo
Yongzhang
Y
D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D043169:Endostatins / Q000737:chemistry* / Q000378:metabolism*; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects; D015202:Protein Engineering; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D043169:Endostatins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014357:Trypsin; D015032:Zinc; D019791:Guanidine