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Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor.
PLoS One. 2011 Apr 28; 6(4):e19253.Plos

Abstract

Both ornithine decarboxylase (ODC) and its regulatory protein, antizyme inhibitor (AZI), can bind with antizyme (AZ), but the latter has a higher AZ-binding affinity. The results of this study clearly identify the critical amino acid residues governing the difference in AZ-binding affinities between human ODC and AZI. Inhibition experiments using a series of ODC mutants suggested that residues 125 and 140 may be the key residues responsible for the differential AZ-binding affinities. The ODC_N125K/M140K double mutant demonstrated a significant inhibition by AZ, and the IC(50) value of this mutant was 0.08 µM, three-fold smaller than that of ODC_WT. Furthermore, the activity of the AZ-inhibited ODC_N125K/M140K enzyme was hardly rescued by AZI. The dissociation constant (K(d)) of the [ODC_N125K/M140K]-AZ heterodimer was approximately 0.02 µM, which is smaller than that of WT_ODC by approximately 10-fold and is very close to the K(d) value of AZI_WT, suggesting that ODC_N125K/M140K has an AZ-binding affinity higher than that of ODC_WT and similar to that of AZI. The efficiency of the AZI_K125N/K140M double mutant in the rescue of AZ-inhibited ODC enzyme activity was less than that of AZI_WT. The K(d) value of [AZI_K125N/K140M]-AZ was 0.18 µM, nine-fold larger than that of AZI_WT and close to the K(d) value of ODC_WT, suggesting that AZI_K125N/K140M has an AZ-binding affinity lower than that of AZI_WT and similar to that of ODC. These data support the hypothesis that the differences in residues 125 and 140 in ODC and AZI are responsible for the differential AZ-binding affinities.

Authors+Show Affiliations

Department of Life Sciences and Institute of Genomics and Bioinformatics, National Chung-Hsing University, Taichung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21552531

Citation

Liu, Yen-Chin, et al. "Critical Factors Governing the Difference in Antizyme-binding Affinities Between Human Ornithine Decarboxylase and Antizyme Inhibitor." PloS One, vol. 6, no. 4, 2011, pp. e19253.
Liu YC, Liu YL, Su JY, et al. Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor. PLoS ONE. 2011;6(4):e19253.
Liu, Y. C., Liu, Y. L., Su, J. Y., Liu, G. Y., & Hung, H. C. (2011). Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor. PloS One, 6(4), e19253. https://doi.org/10.1371/journal.pone.0019253
Liu YC, et al. Critical Factors Governing the Difference in Antizyme-binding Affinities Between Human Ornithine Decarboxylase and Antizyme Inhibitor. PLoS ONE. 2011 Apr 28;6(4):e19253. PubMed PMID: 21552531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor. AU - Liu,Yen-Chin, AU - Liu,Yi-Liang, AU - Su,Jia-Yang, AU - Liu,Guang-Yaw, AU - Hung,Hui-Chih, Y1 - 2011/04/28/ PY - 2010/12/17/received PY - 2011/03/24/accepted PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2011/8/24/medline SP - e19253 EP - e19253 JF - PloS one JO - PLoS ONE VL - 6 IS - 4 N2 - Both ornithine decarboxylase (ODC) and its regulatory protein, antizyme inhibitor (AZI), can bind with antizyme (AZ), but the latter has a higher AZ-binding affinity. The results of this study clearly identify the critical amino acid residues governing the difference in AZ-binding affinities between human ODC and AZI. Inhibition experiments using a series of ODC mutants suggested that residues 125 and 140 may be the key residues responsible for the differential AZ-binding affinities. The ODC_N125K/M140K double mutant demonstrated a significant inhibition by AZ, and the IC(50) value of this mutant was 0.08 µM, three-fold smaller than that of ODC_WT. Furthermore, the activity of the AZ-inhibited ODC_N125K/M140K enzyme was hardly rescued by AZI. The dissociation constant (K(d)) of the [ODC_N125K/M140K]-AZ heterodimer was approximately 0.02 µM, which is smaller than that of WT_ODC by approximately 10-fold and is very close to the K(d) value of AZI_WT, suggesting that ODC_N125K/M140K has an AZ-binding affinity higher than that of ODC_WT and similar to that of AZI. The efficiency of the AZI_K125N/K140M double mutant in the rescue of AZ-inhibited ODC enzyme activity was less than that of AZI_WT. The K(d) value of [AZI_K125N/K140M]-AZ was 0.18 µM, nine-fold larger than that of AZI_WT and close to the K(d) value of ODC_WT, suggesting that AZI_K125N/K140M has an AZ-binding affinity lower than that of AZI_WT and similar to that of ODC. These data support the hypothesis that the differences in residues 125 and 140 in ODC and AZI are responsible for the differential AZ-binding affinities. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21552531/Critical_factors_governing_the_difference_in_antizyme_binding_affinities_between_human_ornithine_decarboxylase_and_antizyme_inhibitor_ L2 - http://dx.plos.org/10.1371/journal.pone.0019253 DB - PRIME DP - Unbound Medicine ER -