The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity

Simon S. Terzyan, Rosa Peracaula, Rafael De Llorens, Yoshiaki Tsushima, Hidenori Yamada, Masaharu Seno, F. Xavier Gomis-Rüth, Miquel Coll

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the χ1 = -72.49°rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the = N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalJournal of Molecular Biology
Volume285
Issue number1
DOIs
Publication statusPublished - Jan 8 1999

Fingerprint

Uridine
Enzymes
Ribonucleases
Hydrogen
Cytidine
Cytosine
Catalysis
Catalytic Domain
Colon
Adenocarcinoma
2-5A-dependent ribonuclease
Cell Line
Peptides

Keywords

  • d(Up) complex
  • Human ribonuclease 4
  • Uracyl specificity
  • X-ray crystal structure

ASJC Scopus subject areas

  • Virology

Cite this

The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity. / Terzyan, Simon S.; Peracaula, Rosa; De Llorens, Rafael; Tsushima, Yoshiaki; Yamada, Hidenori; Seno, Masaharu; Gomis-Rüth, F. Xavier; Coll, Miquel.

In: Journal of Molecular Biology, Vol. 285, No. 1, 08.01.1999, p. 205-214.

Research output: Contribution to journalArticle

Terzyan, Simon S. ; Peracaula, Rosa ; De Llorens, Rafael ; Tsushima, Yoshiaki ; Yamada, Hidenori ; Seno, Masaharu ; Gomis-Rüth, F. Xavier ; Coll, Miquel. / The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity. In: Journal of Molecular Biology. 1999 ; Vol. 285, No. 1. pp. 205-214.
@article{9d65c6cfff3741e9863060814667c3f7,
title = "The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity",
abstract = "The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the χ1 = -72.49°rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the = N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases.",
keywords = "d(Up) complex, Human ribonuclease 4, Uracyl specificity, X-ray crystal structure",
author = "Terzyan, {Simon S.} and Rosa Peracaula and {De Llorens}, Rafael and Yoshiaki Tsushima and Hidenori Yamada and Masaharu Seno and Gomis-R{\"u}th, {F. Xavier} and Miquel Coll",
year = "1999",
month = "1",
day = "8",
doi = "10.1006/jmbi.1998.2288",
language = "English",
volume = "285",
pages = "205--214",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity

AU - Terzyan, Simon S.

AU - Peracaula, Rosa

AU - De Llorens, Rafael

AU - Tsushima, Yoshiaki

AU - Yamada, Hidenori

AU - Seno, Masaharu

AU - Gomis-Rüth, F. Xavier

AU - Coll, Miquel

PY - 1999/1/8

Y1 - 1999/1/8

N2 - The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the χ1 = -72.49°rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the = N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases.

AB - The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the χ1 = -72.49°rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the = N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases.

KW - d(Up) complex

KW - Human ribonuclease 4

KW - Uracyl specificity

KW - X-ray crystal structure

UR - http://www.scopus.com/inward/record.url?scp=0033534398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033534398&partnerID=8YFLogxK

U2 - 10.1006/jmbi.1998.2288

DO - 10.1006/jmbi.1998.2288

M3 - Article

C2 - 9878400

AN - SCOPUS:0033534398

VL - 285

SP - 205

EP - 214

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 1

ER -