Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

22 December 2006

Investigation of the catalytic and structural roles of conserved histidines of human coproporphyrinogen oxidase using site-directed mutagenesis

Shani J. Gitter, Christopher L. Cooper, Jon A. Friesen, Timothy D. Lash, Marjorie A. Jones

Med Sci Monit 2007; 13(1): BR1-10 :: ID: 470138

Abstract

Background: The catalytic contribution of four conserved histidines of human coproporphyrinogen oxidase (CPO) has been investigated using site-directed mutagenesis to change histidine (H) into alanine (A).
Material/Methods: The wild-type and mutant enzyme forms were analyzed for their ability to utilize coproporphyrinogen- III, mesoporphyrinogen-VI, and harderoporphyrinogen as substrates.
Results: Wild-type CPO had specifi c activities of 4.9±0.9 nmole product/min/mg for coproporphyrinogen- III, 1.7±0.7 nmole product/min/mg for mesoporphyrinogen-VI, and 5.1±1.8 nmole product/ min/mg for harderoporphyrinogen. The four mutant enzymes were catalytically competent
with all three substrates, but to varying degrees. The most affected mutant was the H158A enzyme which exhibited approximately 50-fold lower activity than wild-type recombinant CPO.
Conclusions: Thus, His158 of human CPO may have a role in the active site, but none of the conserved histidine residues of human coproporphyrinogen oxidase is essential for catalytic activity although changes in histidines have been implicated in the disease state hereditary coproporphyria.

Keywords: Conserved Sequence, Catalysis, Amino Acid Sequence, Coproporphyrinogen Oxidase - metabolism, Coproporphyrinogens - chemistry, Escherichia coli, Histidine - metabolism, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutant Proteins - metabolism, Oligopeptides, Recombinant Proteins - metabolism, Structure-Activity Relationship

Add Comment 0 Comments

Editorial

01 March 2024 : Editorial  

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia

Dinah V. Parums

DOI: 10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

In Press

18 Mar 2024 : Clinical Research  

Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative Study

Med Sci Monit In Press; DOI: 10.12659/MSM.944136  

0:00

21 Feb 2024 : Clinical Research  

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer

Med Sci Monit In Press; DOI: 10.12659/MSM.943049  

22 Feb 2024 : Review article  

Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943168  

23 Feb 2024 : Clinical Research  

A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943732  

Most Viewed Current Articles

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750