Thermal Stability Properties of A 35-KDa FK506-binding Protein 
of Plasmodium knowlesi

Abstract The FK506-binding protein of Plasmodium knowlesi (Pk-FKBP35) is considerably a viable antimalarial drug target, which belongs to the peptidyl-prolyl cis-trans isomerase (PPIase) protein family member. Structurally, this protein consists of an N-terminal FK506-binding domain (FKBD) and a C-terminal tetratricopeptide repeat domain (TPRD). This study aims to decipher functional properties of these domains as a platform for development of novel antimalarial drugs. Accordingly, full-length Pk-FKBP35 as well as its isolated domains, Pk-FKBD and Pk-TPRD were overexpressed, purified, and characterized. The results showed that catalytic PPIase activity was confined to the full-length Pk-FKBP35 and Pk-FKBD, suggesting that the catalytic activity is structurally regulated by the FKBD. Meanwhile, oligomerization analysis revealed that Pk-TPRD is essential for dimerization. Asp55, Arg60, Trp77 and Phe117 in the Pk-FKBD were considerably important for catalysis as underlined by significant reduction of PPIase activity upon mutations at these residues. Further, inhibition activity of Pk-FKBP35 towards calcineurin phosphatase activity revealed that the presence of FKBD is essential for the inhibitory property, while TPRD may be important for efficient binding to calcineurin. We then discussed possible roles of FKBP35 in Plasmodium cells and proposed mechanisms by which the immunosuppressive drug, FK506, interacts with the protein.

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Autoantibodies to FK506 Binding Protein 12 (FKBP12) in Autoimmune Diseases

Autoimmunity ◽

10.3109/08916939908998531 ◽

1999 ◽

Vol 29 (3) ◽

pp. 159-170 ◽

Cited By ~ 6

Author(s):

Nobuhiko Shinkura ◽

Iwao Ikai ◽

Akira Yamauchl ◽

Tetsuro Hirose ◽

Yasuhiro Kawap ◽

...

Keyword(s):

Autoimmune Diseases ◽

Binding Protein ◽

Fk506 Binding Protein

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slyD, a host gene required for phi X174 lysis, is related to the FK506-binding protein family of peptidyl-prolyl cis-trans-isomerases.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)42027-8 ◽

1994 ◽

Vol 269 (4) ◽

pp. 2902-2910 ◽

Cited By ~ 1

Author(s):

W.D. Roof ◽

S.M. Horne ◽

K.D. Young ◽

R. Young

Keyword(s):

Binding Protein ◽

Protein Family ◽

Host Gene ◽

Fk506 Binding Protein

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FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma

Journal of International Medical Research ◽

10.1177/03000605211008325 ◽

2021 ◽

Vol 49 (4) ◽

pp. 030006052110083

Author(s):

Zhenya Gao ◽

Fang Yu ◽

Huanxia Jia ◽

Zhuo Ye ◽

Shijie Yao

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Binding Protein ◽

Progression Free Survival ◽

Papillary Thyroid ◽

Expression Levels ◽

Fk506 Binding Protein ◽

Normal Tissues ◽

Induced Apoptosis

Objective To detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC. Methods FKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice. Results We revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice. Conclusions The results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.

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Disrupting Function of FK506-Binding Protein 1b/12.6 Induces the Ca2+-Dysregulation Aging Phenotype in Hippocampal Neurons

Journal of Neuroscience ◽

10.1523/jneurosci.4805-10.2011 ◽

2011 ◽

Vol 31 (5) ◽

pp. 1693-1703 ◽

Cited By ~ 36

Author(s):

J. C. Gant ◽

K.-C. Chen ◽

C. M. Norris ◽

I. Kadish ◽

O. Thibault ◽

...

Keyword(s):

Hippocampal Neurons ◽

Binding Protein ◽

Fk506 Binding Protein

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EPH receptor B2 (EPHB2); FK506 binding protein 5 (FKBP5)

Science-Business eXchange ◽

10.1038/scibx.2011.488 ◽

2011 ◽

Vol 4 (17) ◽

pp. 488-488

Keyword(s):

Binding Protein ◽

Eph Receptor ◽

Fk506 Binding Protein

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Sex-related effects on diabetes-induced alterations in calcium release in the rat heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00619.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. H3584-H3592 ◽

Cited By ~ 21

Author(s):

Nazmi Yaras ◽

Erkan Tuncay ◽

Nuhan Purali ◽

Babur Sahinoglu ◽

Guy Vassort ◽

...

Keyword(s):

Calcium Release ◽

Binding Protein ◽

Ryanodine Receptors ◽

Left Ventricular ◽

Adult Rats ◽

Fk506 Binding Protein ◽

Pressure Development ◽

Spatiotemporal Parameters ◽

Intracellular Ca ◽

Developed Pressure

The present study was designed to determine whether the properties of local Ca2+ release and its related regulatory mechanisms might provide insight into the role of sex differences in heart functions of control and streptozotocin-induced diabetic adult rats. Left ventricular developed pressure, the rates of pressure development and decay (±dP/d t), basal intracellular Ca2+ level ([Ca2+]i), and spatiotemporal parameters of [Ca2+]i transients were found to be similar in male and female control rats. However, spatiotemporal parameters of Ca2+ sparks in cardiomyocytes isolated from control females were significantly larger and slower than those in control males. Diabetes reduced left ventricular developed pressure to a lower extent in females than in males, and the diabetes-induced depressions in both +dP/d t and −dP/d t were less in females than in males. Diabetes elicited a smaller reduction in the amplitude of [Ca2+]i transients in females than in males, a smaller reduction in sarcoplasmic reticulum-Ca2+ load, and less increase in basal [Ca2+]i. Similarly, the elementary Ca2+ events and their control proteins were clearly different in both sexes, and these differences were more marked in diabetes. Diabetes-induced depression of the Ca2+ spark amplitude was significantly less in females than in matched males. Levels of cardiac ryanodine receptors (RyR2) and FK506-binding protein 12.6 in control females were significantly higher than those shown in control males. Diabetes induced less RyR2 phosphorylation and FK506-binding protein 12.6 unbinding in females. Moreover, total and free sulfhydryl groups were significantly less reduced, and PKC levels were less increased, in diabetic females than in diabetic males. The present data related to local Ca2+ release and its related proteins describe some of the mechanisms that may underlie sex-related differences accounting for females to have less frequent development of cardiac diseases.

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