Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site

Sydney P. Craig; Pamela J. Focia; Robert J. Fletterick

doi:10.1016/S0167-4838(97)00037-X

Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site

Sydney P. Craig^*, Pamela J. Focia, Robert J. Fletterick

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Lysine was substituted for a conserved arginine at position 199 of the schistosomal hypoxanthine phosphoribosyltransferase (HPRT). This resulted in a ≤ 35-fold increase in the K(M) for binding phosphoribosyl-pyrophosphate (PRPP). The possible functional role of R199 in tertiary structure, as well as in the binding of PRPP, is interpreted in the context of the reported three dimensional structure for the human HPRT.

Original language	English (US)
Pages (from-to)	1-3
Number of pages	3
Journal	Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Volume	1339
Issue number	1
DOIs	https://doi.org/10.1016/S0167-4838(97)00037-X
State	Published - Apr 25 1997

Funding

The R199K mutation was generated by SPCIII while working in C.C. Wang's laboratory at UCSF. We are grateful to C.C. for granting us permission to continue investigating this site directed mutant form of the schistosomal enzyme. We thank Xiao Qing Lin for technical contributions and are grateful to Janina Eads and James C. Sacchettini of the Albert Einstein College of Medicine for generously providing us with the 3-D coordinates for dimers of the human HPRT. This work was partially supported by NIH Grant AI34326 to S.P.C.

Keywords

Mutagenesis
Phosphoribosyltransferase
Structure

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology

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10.1016/S0167-4838(97)00037-X

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title = "Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site",

abstract = "Lysine was substituted for a conserved arginine at position 199 of the schistosomal hypoxanthine phosphoribosyltransferase (HPRT). This resulted in a ≤ 35-fold increase in the K(M) for binding phosphoribosyl-pyrophosphate (PRPP). The possible functional role of R199 in tertiary structure, as well as in the binding of PRPP, is interpreted in the context of the reported three dimensional structure for the human HPRT.",

keywords = "Mutagenesis, Phosphoribosyltransferase, Structure",

author = "Craig, {Sydney P.} and Focia, {Pamela J.} and Fletterick, {Robert J.}",

note = "Funding Information: The R199K mutation was generated by SPCIII while working in C.C. Wang's laboratory at UCSF. We are grateful to C.C. for granting us permission to continue investigating this site directed mutant form of the schistosomal enzyme. We thank Xiao Qing Lin for technical contributions and are grateful to Janina Eads and James C. Sacchettini of the Albert Einstein College of Medicine for generously providing us with the 3-D coordinates for dimers of the human HPRT. This work was partially supported by NIH Grant AI34326 to S.P.C. ",

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doi = "10.1016/S0167-4838(97)00037-X",

language = "English (US)",

volume = "1339",

pages = "1--3",

journal = "Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology",

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Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site. / Craig, Sydney P.; Focia, Pamela J.; Fletterick, Robert J.
In: Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology, Vol. 1339, No. 1, 25.04.1997, p. 1-3.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site

AU - Craig, Sydney P.

AU - Focia, Pamela J.

AU - Fletterick, Robert J.

N1 - Funding Information: The R199K mutation was generated by SPCIII while working in C.C. Wang's laboratory at UCSF. We are grateful to C.C. for granting us permission to continue investigating this site directed mutant form of the schistosomal enzyme. We thank Xiao Qing Lin for technical contributions and are grateful to Janina Eads and James C. Sacchettini of the Albert Einstein College of Medicine for generously providing us with the 3-D coordinates for dimers of the human HPRT. This work was partially supported by NIH Grant AI34326 to S.P.C.

PY - 1997/4/25

Y1 - 1997/4/25

N2 - Lysine was substituted for a conserved arginine at position 199 of the schistosomal hypoxanthine phosphoribosyltransferase (HPRT). This resulted in a ≤ 35-fold increase in the K(M) for binding phosphoribosyl-pyrophosphate (PRPP). The possible functional role of R199 in tertiary structure, as well as in the binding of PRPP, is interpreted in the context of the reported three dimensional structure for the human HPRT.

AB - Lysine was substituted for a conserved arginine at position 199 of the schistosomal hypoxanthine phosphoribosyltransferase (HPRT). This resulted in a ≤ 35-fold increase in the K(M) for binding phosphoribosyl-pyrophosphate (PRPP). The possible functional role of R199 in tertiary structure, as well as in the binding of PRPP, is interpreted in the context of the reported three dimensional structure for the human HPRT.

KW - Mutagenesis

KW - Phosphoribosyltransferase

KW - Structure

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Substitution of lysine for arginine at position 199 of a hypoxanthine phosphoribosyltransferase interferes with binding of the primary substrate to the active site

Abstract

Funding

Keywords

ASJC Scopus subject areas

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