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The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound.
Biochem Biophys Res Commun. 2022 07 30; 615:63-69.BB

Abstract

HucR is a MarR family protein of Deinococcus radiodurans, which binds tightly to the intergenic region of HucR and the uricase gene to inhibit their expression. Urate (or uric acid) antagonizes the repressor function of HucR by binding to HucR to impede its association with the cognate DNA. The previously reported crystal structure of HucR was without the bound urate showing significant structural homology to other MarR structures. In this paper, we report the crystal structure of HucR determined with the urate bound. However, despite the fact that the urate is found at a site well-known to harbor ligands in other MarR family proteins, the overall HucR structure indicates that no significant change in structure takes place with the urate bound. Structure analysis further suggests that the urate interaction in HucR is mediated by histidine/glutamate side chains and ordered water molecules stabilized by various residues. Such interaction is quite unique compared to other known structural interactions between urate and its binding proteins. Furthermore, structural comparison of the apo- and the urate bound forms allows us to hypothesize that the Trp20-mediated water network in the apo-form stabilizes the proper HucR fold for cognate DNA binding, and that urate binding, also via Trp20, and the consequent reorganization of water molecules in the binding pocket, likely disrupts the DNA binding configuration to result in the attenuated DNA binding.

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Publisher Full Text (DOI)

Authors+Show Affiliations

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea.

Research Institute, National Cancer Center Korea, Goyang, Gyeonggi, Republic of Korea.

Research Institute, National Cancer Center Korea, Goyang, Gyeonggi, Republic of Korea.

Chemistry and Biochemistry Department, California Polytechnic State University, San Luis Obispo, CA, USA.

School of Systems Biomedical Science and Integrative Institute of Basic Sciences, Soongsil University, Seoul, Republic of Korea. Electronic address: psy@ssu.ac.kr.

MeSH

Bacterial ProteinsCrystallography, X-RayDNADeinococcusProtein BindingUric AcidWater

Pub Type(s)

Journal Article

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

Language

eng

PubMed ID

35605407

Citation

Rho, SooHo, et al. "The Structure of Deinococcus Radiodurans Transcriptional Regulator HucR Retold With the Urate Bound." Biochemical and Biophysical Research Communications, vol. 615, 2022, pp. 63-69.

Rho S, Jung W, Park JK, et al. The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound. Biochem Biophys Res Commun. 2022;615:63-69.

Rho, S., Jung, W., Park, J. K., Choi, M. H., Kim, M., Kim, J., Byun, J., Park, T., Lee, B. I., Wilkinson, S. P., & Park, S. (2022). The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound. Biochemical and Biophysical Research Communications, 615, 63-69. https://doi.org/10.1016/j.bbrc.2022.05.034

Rho S, et al. The Structure of Deinococcus Radiodurans Transcriptional Regulator HucR Retold With the Urate Bound. Biochem Biophys Res Commun. 2022 07 30;615:63-69. PubMed PMID: 35605407.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound. AU - Rho,SooHo, AU - Jung,WeonSeok, AU - Park,Jeong Kuk, AU - Choi,Min Hee, AU - Kim,MinJu, AU - Kim,JooYoung, AU - Byun,JiWon, AU - Park,Taehyun, AU - Lee,Byung Il, AU - Wilkinson,Steven P, AU - Park,SangYoun, Y1 - 2022/05/13/ PY - 2022/04/21/received PY - 2022/04/28/revised PY - 2022/05/11/accepted PY - 2022/5/24/pubmed PY - 2022/6/22/medline PY - 2022/5/23/entrez KW - HucR KW - MarR KW - Repressor KW - Urate KW - Uric acid KW - X-ray crystallography SP - 63 EP - 69 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 615 N2 - HucR is a MarR family protein of Deinococcus radiodurans, which binds tightly to the intergenic region of HucR and the uricase gene to inhibit their expression. Urate (or uric acid) antagonizes the repressor function of HucR by binding to HucR to impede its association with the cognate DNA. The previously reported crystal structure of HucR was without the bound urate showing significant structural homology to other MarR structures. In this paper, we report the crystal structure of HucR determined with the urate bound. However, despite the fact that the urate is found at a site well-known to harbor ligands in other MarR family proteins, the overall HucR structure indicates that no significant change in structure takes place with the urate bound. Structure analysis further suggests that the urate interaction in HucR is mediated by histidine/glutamate side chains and ordered water molecules stabilized by various residues. Such interaction is quite unique compared to other known structural interactions between urate and its binding proteins. Furthermore, structural comparison of the apo- and the urate bound forms allows us to hypothesize that the Trp20-mediated water network in the apo-form stabilizes the proper HucR fold for cognate DNA binding, and that urate binding, also via Trp20, and the consequent reorganization of water molecules in the binding pocket, likely disrupts the DNA binding configuration to result in the attenuated DNA binding. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/35605407/The_structure_of_Deinococcus_radiodurans_transcriptional_regulator_HucR_retold_with_the_urate_bound_ DB - PRIME DP - Unbound Medicine ER -