title: Kinetics of Zn(2+)-induced brain type creatine kinase unfolding and aggregation.
abstract: We studied the effect of Zn(2+) on the folding and aggregation of brain creatine kinase (CK-BB). We developed a method to purify CK-BB from rabbit brain and conducted inhibition kinetics and unfolding studies of CK-BB. Zn(2+) conspicuously aggregated and osmolytes, such as glycine and proline, were able to suppress the formation of aggregates and protect the enzymatic activity against Zn(2+). These results suggest that Zn(2+) might act as a risk factor for CK-BB in the brain under certain conditions, and some osmolytes may help CK-BB to sustain the active state when Zn(2+) is present. Our study provides useful information regarding the effect of Zn(2+) on brain-derived metabolic enzymes, especially those that are putatively related to brain disease. Furthermore, our study suggests that although Zn(2+) may induce CK-BB inactivation and misfolding, the ability of some abundant proteins and osmolytes to chelate Zn(2+) nonspecifically may protect CK-BB and allow it to exist in the active form.
authors.affiliation: Department of Biological Science and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Mu
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Lü
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Byoung-Chul
authors.initials: BC
authors.lastname: Kim
authors.forename: Jong
authors.initials: J
authors.lastname: Bhak
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
authors.forename: He-Chang
authors.initials: HC
authors.lastname: Zou
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D052276:Creatine Kinase, BB Form / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005453:Fluorescence; D005998:Glycine / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D011392:Proline / Q000494:pharmacology; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology*
chemical_list: D011392:Proline; D052276:Creatine Kinase, BB Form; D015032:Zinc; D005998:Glycine