2.6 Å X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase

Peter Smith, Bingsen Zhou, Nam Ho, Yate Ching Yuan, Leila Su, Shiou Chuan Tsai, Yun Yen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Human p53R2 (hp53R2) is a 351-residue p53-inducible ribonucleotide reductase (RNR) small subunit. It shares >80% sequence identity with hRRM2, the small RNR subunit responsible for normal maintenance of the deoxyribonucleotide (dNTP) pool used for DNA replication, which is active during the S phase in a cell cycle-dependent fashion. But rather than cyclic dNTP synthesis, hp53R2 has been shown to supply dNTPs forDNA repair to cells in G0-G1 in a p53-dependent fashion. The first X-ray crystal structure of hp53R2 is determined to 2.6 Å, in which monomers A and B exhibit mono- and binuclear iron occupancy, respectively. The pronounced structural differences at three regions between hp53R2 and hRRM2 highlight the possible regulatory role in iron assimilation and help explain previously observed physical and biochemical differences in the mobility and accessibility of the radical iron center, as well as radical transfer pathways between the two enzymes. The sequence-structure-function correlations that differentiate hp53R2 and hRRM2 are revealed for the first time. Insight gained fromthis structural work will be used in the identification of biological function, regulation mechanism, and inhibitor selection in RNR small subunits.

Original languageEnglish
Pages (from-to)11134-11141
Number of pages8
JournalBiochemistry
Volume48
Issue number46
DOIs
Publication statusPublished - Nov 24 2009
Externally publishedYes

Fingerprint

Ribonucleotide Reductases
Iron
Crystal structure
X-Rays
X rays
Deoxyribonucleotides
Repair
Monomers
Cells
DNA Replication
S Phase
DNA
Enzymes
Cell Cycle
Maintenance

ASJC Scopus subject areas

  • Biochemistry

Cite this

2.6 Å X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase. / Smith, Peter; Zhou, Bingsen; Ho, Nam; Yuan, Yate Ching; Su, Leila; Tsai, Shiou Chuan; Yen, Yun.

In: Biochemistry, Vol. 48, No. 46, 24.11.2009, p. 11134-11141.

Research output: Contribution to journalArticle

Smith, P, Zhou, B, Ho, N, Yuan, YC, Su, L, Tsai, SC & Yen, Y 2009, '2.6 Å X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase', Biochemistry, vol. 48, no. 46, pp. 11134-11141. https://doi.org/10.1021/bi9001425
Smith P, Zhou B, Ho N, Yuan YC, Su L, Tsai SC et al. 2.6 Å X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase. Biochemistry. 2009 Nov 24;48(46):11134-11141. https://doi.org/10.1021/bi9001425
Smith, Peter ; Zhou, Bingsen ; Ho, Nam ; Yuan, Yate Ching ; Su, Leila ; Tsai, Shiou Chuan ; Yen, Yun. / 2.6 Å X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase. In: Biochemistry. 2009 ; Vol. 48, No. 46. pp. 11134-11141.
@article{b0bb37ec9d644e188a59812ae2b91108,
title = "2.6 {\AA} X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase",
abstract = "Human p53R2 (hp53R2) is a 351-residue p53-inducible ribonucleotide reductase (RNR) small subunit. It shares >80{\%} sequence identity with hRRM2, the small RNR subunit responsible for normal maintenance of the deoxyribonucleotide (dNTP) pool used for DNA replication, which is active during the S phase in a cell cycle-dependent fashion. But rather than cyclic dNTP synthesis, hp53R2 has been shown to supply dNTPs forDNA repair to cells in G0-G1 in a p53-dependent fashion. The first X-ray crystal structure of hp53R2 is determined to 2.6 {\AA}, in which monomers A and B exhibit mono- and binuclear iron occupancy, respectively. The pronounced structural differences at three regions between hp53R2 and hRRM2 highlight the possible regulatory role in iron assimilation and help explain previously observed physical and biochemical differences in the mobility and accessibility of the radical iron center, as well as radical transfer pathways between the two enzymes. The sequence-structure-function correlations that differentiate hp53R2 and hRRM2 are revealed for the first time. Insight gained fromthis structural work will be used in the identification of biological function, regulation mechanism, and inhibitor selection in RNR small subunits.",
author = "Peter Smith and Bingsen Zhou and Nam Ho and Yuan, {Yate Ching} and Leila Su and Tsai, {Shiou Chuan} and Yun Yen",
year = "2009",
month = "11",
day = "24",
doi = "10.1021/bi9001425",
language = "English",
volume = "48",
pages = "11134--11141",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "46",

}

TY - JOUR

T1 - 2.6 Å X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase

AU - Smith, Peter

AU - Zhou, Bingsen

AU - Ho, Nam

AU - Yuan, Yate Ching

AU - Su, Leila

AU - Tsai, Shiou Chuan

AU - Yen, Yun

PY - 2009/11/24

Y1 - 2009/11/24

N2 - Human p53R2 (hp53R2) is a 351-residue p53-inducible ribonucleotide reductase (RNR) small subunit. It shares >80% sequence identity with hRRM2, the small RNR subunit responsible for normal maintenance of the deoxyribonucleotide (dNTP) pool used for DNA replication, which is active during the S phase in a cell cycle-dependent fashion. But rather than cyclic dNTP synthesis, hp53R2 has been shown to supply dNTPs forDNA repair to cells in G0-G1 in a p53-dependent fashion. The first X-ray crystal structure of hp53R2 is determined to 2.6 Å, in which monomers A and B exhibit mono- and binuclear iron occupancy, respectively. The pronounced structural differences at three regions between hp53R2 and hRRM2 highlight the possible regulatory role in iron assimilation and help explain previously observed physical and biochemical differences in the mobility and accessibility of the radical iron center, as well as radical transfer pathways between the two enzymes. The sequence-structure-function correlations that differentiate hp53R2 and hRRM2 are revealed for the first time. Insight gained fromthis structural work will be used in the identification of biological function, regulation mechanism, and inhibitor selection in RNR small subunits.

AB - Human p53R2 (hp53R2) is a 351-residue p53-inducible ribonucleotide reductase (RNR) small subunit. It shares >80% sequence identity with hRRM2, the small RNR subunit responsible for normal maintenance of the deoxyribonucleotide (dNTP) pool used for DNA replication, which is active during the S phase in a cell cycle-dependent fashion. But rather than cyclic dNTP synthesis, hp53R2 has been shown to supply dNTPs forDNA repair to cells in G0-G1 in a p53-dependent fashion. The first X-ray crystal structure of hp53R2 is determined to 2.6 Å, in which monomers A and B exhibit mono- and binuclear iron occupancy, respectively. The pronounced structural differences at three regions between hp53R2 and hRRM2 highlight the possible regulatory role in iron assimilation and help explain previously observed physical and biochemical differences in the mobility and accessibility of the radical iron center, as well as radical transfer pathways between the two enzymes. The sequence-structure-function correlations that differentiate hp53R2 and hRRM2 are revealed for the first time. Insight gained fromthis structural work will be used in the identification of biological function, regulation mechanism, and inhibitor selection in RNR small subunits.

UR - http://www.scopus.com/inward/record.url?scp=72749119232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72749119232&partnerID=8YFLogxK

U2 - 10.1021/bi9001425

DO - 10.1021/bi9001425

M3 - Article

C2 - 19728742

AN - SCOPUS:72749119232

VL - 48

SP - 11134

EP - 11141

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 46

ER -