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Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function.
Protein Sci. 2008 May; 17(5):793-802.PS

Abstract

Antizyme inhibitor (AzI) regulates cellular polyamine homeostasis by binding to the polyamine-induced protein, Antizyme (Az), with greater affinity than ornithine decarboxylase (ODC). AzI is highly homologous to ODC but is not enzymatically active. In order to understand these specific characteristics of AzI and its differences from ODC, we determined the 3D structure of mouse AzI to 2.05 A resolution. Both AzI and ODC crystallize as a dimer. However, fewer interactions at the dimer interface, a smaller buried surface area, and lack of symmetry of the interactions between residues from the two monomers in the AzI structure suggest that this dimeric structure is nonphysiological. In addition, the absence of residues and interactions required for pyridoxal 5'-phosphate (PLP) binding suggests that AzI does not bind PLP. Biochemical studies confirmed the lack of PLP binding and revealed that AzI exists as a monomer in solution while ODC is dimeric. Our findings that AzI exists as a monomer and is unable to bind PLP provide two independent explanations for its lack of enzymatic activity and suggest the basis for its enhanced affinity toward Az.

Authors+Show Affiliations

The Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot 76100, Israel.No affiliation info availableNo 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

18369191

Citation

Albeck, Shira, et al. "Crystallographic and Biochemical Studies Revealing the Structural Basis for Antizyme Inhibitor Function." Protein Science : a Publication of the Protein Society, vol. 17, no. 5, 2008, pp. 793-802.
Albeck S, Dym O, Unger T, et al. Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function. Protein Sci. 2008;17(5):793-802.
Albeck, S., Dym, O., Unger, T., Snapir, Z., Bercovich, Z., & Kahana, C. (2008). Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function. Protein Science : a Publication of the Protein Society, 17(5), 793-802. https://doi.org/10.1110/ps.073427208
Albeck S, et al. Crystallographic and Biochemical Studies Revealing the Structural Basis for Antizyme Inhibitor Function. Protein Sci. 2008;17(5):793-802. PubMed PMID: 18369191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function. AU - Albeck,Shira, AU - Dym,Orly, AU - Unger,Tamar, AU - Snapir,Zohar, AU - Bercovich,Zippy, AU - Kahana,Chaim, Y1 - 2008/03/27/ PY - 2008/3/29/pubmed PY - 2008/5/24/medline PY - 2008/3/29/entrez SP - 793 EP - 802 JF - Protein science : a publication of the Protein Society JO - Protein Sci. VL - 17 IS - 5 N2 - Antizyme inhibitor (AzI) regulates cellular polyamine homeostasis by binding to the polyamine-induced protein, Antizyme (Az), with greater affinity than ornithine decarboxylase (ODC). AzI is highly homologous to ODC but is not enzymatically active. In order to understand these specific characteristics of AzI and its differences from ODC, we determined the 3D structure of mouse AzI to 2.05 A resolution. Both AzI and ODC crystallize as a dimer. However, fewer interactions at the dimer interface, a smaller buried surface area, and lack of symmetry of the interactions between residues from the two monomers in the AzI structure suggest that this dimeric structure is nonphysiological. In addition, the absence of residues and interactions required for pyridoxal 5'-phosphate (PLP) binding suggests that AzI does not bind PLP. Biochemical studies confirmed the lack of PLP binding and revealed that AzI exists as a monomer in solution while ODC is dimeric. Our findings that AzI exists as a monomer and is unable to bind PLP provide two independent explanations for its lack of enzymatic activity and suggest the basis for its enhanced affinity toward Az. SN - 1469-896X UR - https://www.unboundmedicine.com/medline/citation/18369191/Crystallographic_and_biochemical_studies_revealing_the_structural_basis_for_antizyme_inhibitor_function_ L2 - https://doi.org/10.1110/ps.073427208 DB - PRIME DP - Unbound Medicine ER -