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International Journal of Molecular Medicine
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Print ISSN: 1107-3756 Online ISSN: 1791-244X
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March 2009 Volume 23 Issue 3

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

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Article

Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1

  • Authors:
    • Wen-Pu Zhou
    • Wen-Wei Zhong
    • Xue-Hong Zhang
    • Jian-ping Ding
    • Zi-Li Zhang
    • Zhen-Wei Xia

  • View Affiliations / Copyright

    Affiliations: Ruijin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
  • Pages: 379-387
    |
    Published online on: March 1, 2009
       https://doi.org/10.3892/ijmm_00000142
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Abstract

Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 Å, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 Å, and the standard bond angle deviation was 1.3°. The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored ≈90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis.

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Copy and paste a formatted citation
Spandidos Publications style
Zhou W, Zhong W, Zhang X, Ding J, Zhang Z and Xia Z: Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1. Int J Mol Med 23: 379-387, 2009.
APA
Zhou, W., Zhong, W., Zhang, X., Ding, J., Zhang, Z., & Xia, Z. (2009). Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1. International Journal of Molecular Medicine, 23, 379-387. https://doi.org/10.3892/ijmm_00000142
MLA
Zhou, W., Zhong, W., Zhang, X., Ding, J., Zhang, Z., Xia, Z."Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1". International Journal of Molecular Medicine 23.3 (2009): 379-387.
Chicago
Zhou, W., Zhong, W., Zhang, X., Ding, J., Zhang, Z., Xia, Z."Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1". International Journal of Molecular Medicine 23, no. 3 (2009): 379-387. https://doi.org/10.3892/ijmm_00000142
Copy and paste a formatted citation
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Spandidos Publications style
Zhou W, Zhong W, Zhang X, Ding J, Zhang Z and Xia Z: Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1. Int J Mol Med 23: 379-387, 2009.
APA
Zhou, W., Zhong, W., Zhang, X., Ding, J., Zhang, Z., & Xia, Z. (2009). Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1. International Journal of Molecular Medicine, 23, 379-387. https://doi.org/10.3892/ijmm_00000142
MLA
Zhou, W., Zhong, W., Zhang, X., Ding, J., Zhang, Z., Xia, Z."Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1". International Journal of Molecular Medicine 23.3 (2009): 379-387.
Chicago
Zhou, W., Zhong, W., Zhang, X., Ding, J., Zhang, Z., Xia, Z."Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1". International Journal of Molecular Medicine 23, no. 3 (2009): 379-387. https://doi.org/10.3892/ijmm_00000142
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