Comparing the human and schistosomal hypoxanthine-guanine phosphoribosyltransferases by circular dichroism

Ling Yuan, Chuen Shang C. Wu, Sydney P. Craig, Angela F. Liu, Ching C. Wang

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15 Scopus citations

Abstract

The hypoxanthine-guanine phosphoribosyltransferases (HGPRTases) of human and the parasitic trematode, Schistosoma mansoni, are of biomedical importance. The conformations of these two enzymes were studied by circular dichroism (CD). The schistosomal HGPRTase is estimated to contain 27% α-helix and 30% β-structure. This result is consistent with what is predicted from a tertiary model (Craig, S.P., Cohen, F.E., Yuan, L., McKerrow, J.H. and Wang, C.C. (1991) in Molecular & Immunological Aspects of Parasitism (Wang, C.C., ed.), pp. 122-138, Am. Assoc. Adv. Sci., Washington DC, USA), which proposes that the enzyme is an alpha/beta barrel protein. The human enzyme is estimated to contain 21% α-helix and 53% β-form. The two enzymes are different in their thermostability. The human enzyme remains active after being heated to 85°C for 15 min, while the schistosomal enzyme only retains its activity at temperature below 65°C. The transition temperature (T1/2) of the schistosomal HGPRTase was determined by CD measurement to be 57.5°C. One of the enzyme substrates, phosphoribose pyrophosphate (PRPP), stabilizes the HGPRTases by preventing the human enzyme from unfolding at 85°C and partially protecting the schistosomal enzyme from unfolding at 65°C. It is suggested that the amino-acid substitutions in the human enzyme improve the spatial structure and stability of its α-helices, which may lead to an enhanced thermostability.

Original languageEnglish
Pages (from-to)10-16
Number of pages7
JournalBBA - Protein Structure
Volume1162
Issue number1-2
DOIs
StatePublished - Mar 5 1993

Bibliographical note

Funding Information:
This study is supported by NIH grants number AI-24011 (to C.C.W.), GM-10880 (to C.S-C.W. and J.T.Y.) and the Biotechnology Grant for Protein Crystallization from the State of California/UCSF (to L.Y.). We thank Dr. Fred E. Cohen for his valuable suggestions and Drs. James H. McKerrow and Douglas A. Kuntz for their critical reading of the manuscript.

Keywords

  • Circular dichroism
  • Heat stable protein
  • Hypoxanthine-guanine phosphoribosyltransferase
  • Protein conformation

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology

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