Three-dimensional models of proteases involved in patterning of the drosophila embryo: Crucial role of predicted cation binding sites

Thierry Rose, Ellen LeMosy, Angelene M. Cantwell, Dolly Banerjee-Roy, James B. Skeath, Enrico Di Cera

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Three-dimensional models of the catalytic domains of Nudel (Ndl), Gastrulation Defective (Gd), Snake (Snk), and Easter (Ea), and their complexes with substrate suggest a possible organization of the enzyme cascade controlling the dorsoventral fate of the fruit fly embryo. The models predict that Gd activates Snk, which in turn activates Ea. Gd can be activated either autoproteolytically or by Ndl. The three-dimensional models of each enzyme-substrate complex in the cascade rationalize existing mutagenesis data and the associated phenotypes. The models also predict unanticipated features like a Ca2+ binding site in Ea and a Na+ binding site in Ndl and Gd. These binding sites are likely to play a crucial role in vivo as suggested by mutant enzymes introduced into embryos as mRNAs. The mutations in Gd that eliminate Na+ binding cause an apparent increase in activity, whereas mutations in Ea that abrogate Ca2+ binding result in complete loss of activity. A mutation in Ea predicted to introduce Na+ binding results in apparently increased activity with ventralization of the embryo, an effect not observed with wild-type Ea mRNA.

Original languageEnglish (US)
Pages (from-to)11320-11330
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number13
DOIs
StatePublished - Mar 28 2003

Fingerprint

Gastrulation
Drosophila
Cations
Peptide Hydrolases
Embryonic Structures
Binding Sites
Snakes
Enzymes
Mutation
Mutagenesis
Messenger RNA
Substrates
Fruits
Diptera
Fruit
Catalytic Domain
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Three-dimensional models of proteases involved in patterning of the drosophila embryo : Crucial role of predicted cation binding sites. / Rose, Thierry; LeMosy, Ellen; Cantwell, Angelene M.; Banerjee-Roy, Dolly; Skeath, James B.; Di Cera, Enrico.

In: Journal of Biological Chemistry, Vol. 278, No. 13, 28.03.2003, p. 11320-11330.

Research output: Contribution to journalArticle

Rose, Thierry ; LeMosy, Ellen ; Cantwell, Angelene M. ; Banerjee-Roy, Dolly ; Skeath, James B. ; Di Cera, Enrico. / Three-dimensional models of proteases involved in patterning of the drosophila embryo : Crucial role of predicted cation binding sites. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 13. pp. 11320-11330.
@article{80c5788661184ae3ba8f701e68d8feb2,
title = "Three-dimensional models of proteases involved in patterning of the drosophila embryo: Crucial role of predicted cation binding sites",
abstract = "Three-dimensional models of the catalytic domains of Nudel (Ndl), Gastrulation Defective (Gd), Snake (Snk), and Easter (Ea), and their complexes with substrate suggest a possible organization of the enzyme cascade controlling the dorsoventral fate of the fruit fly embryo. The models predict that Gd activates Snk, which in turn activates Ea. Gd can be activated either autoproteolytically or by Ndl. The three-dimensional models of each enzyme-substrate complex in the cascade rationalize existing mutagenesis data and the associated phenotypes. The models also predict unanticipated features like a Ca2+ binding site in Ea and a Na+ binding site in Ndl and Gd. These binding sites are likely to play a crucial role in vivo as suggested by mutant enzymes introduced into embryos as mRNAs. The mutations in Gd that eliminate Na+ binding cause an apparent increase in activity, whereas mutations in Ea that abrogate Ca2+ binding result in complete loss of activity. A mutation in Ea predicted to introduce Na+ binding results in apparently increased activity with ventralization of the embryo, an effect not observed with wild-type Ea mRNA.",
author = "Thierry Rose and Ellen LeMosy and Cantwell, {Angelene M.} and Dolly Banerjee-Roy and Skeath, {James B.} and {Di Cera}, Enrico",
year = "2003",
month = "3",
day = "28",
doi = "10.1074/jbc.M211820200",
language = "English (US)",
volume = "278",
pages = "11320--11330",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

TY - JOUR

T1 - Three-dimensional models of proteases involved in patterning of the drosophila embryo

T2 - Crucial role of predicted cation binding sites

AU - Rose, Thierry

AU - LeMosy, Ellen

AU - Cantwell, Angelene M.

AU - Banerjee-Roy, Dolly

AU - Skeath, James B.

AU - Di Cera, Enrico

PY - 2003/3/28

Y1 - 2003/3/28

N2 - Three-dimensional models of the catalytic domains of Nudel (Ndl), Gastrulation Defective (Gd), Snake (Snk), and Easter (Ea), and their complexes with substrate suggest a possible organization of the enzyme cascade controlling the dorsoventral fate of the fruit fly embryo. The models predict that Gd activates Snk, which in turn activates Ea. Gd can be activated either autoproteolytically or by Ndl. The three-dimensional models of each enzyme-substrate complex in the cascade rationalize existing mutagenesis data and the associated phenotypes. The models also predict unanticipated features like a Ca2+ binding site in Ea and a Na+ binding site in Ndl and Gd. These binding sites are likely to play a crucial role in vivo as suggested by mutant enzymes introduced into embryos as mRNAs. The mutations in Gd that eliminate Na+ binding cause an apparent increase in activity, whereas mutations in Ea that abrogate Ca2+ binding result in complete loss of activity. A mutation in Ea predicted to introduce Na+ binding results in apparently increased activity with ventralization of the embryo, an effect not observed with wild-type Ea mRNA.

AB - Three-dimensional models of the catalytic domains of Nudel (Ndl), Gastrulation Defective (Gd), Snake (Snk), and Easter (Ea), and their complexes with substrate suggest a possible organization of the enzyme cascade controlling the dorsoventral fate of the fruit fly embryo. The models predict that Gd activates Snk, which in turn activates Ea. Gd can be activated either autoproteolytically or by Ndl. The three-dimensional models of each enzyme-substrate complex in the cascade rationalize existing mutagenesis data and the associated phenotypes. The models also predict unanticipated features like a Ca2+ binding site in Ea and a Na+ binding site in Ndl and Gd. These binding sites are likely to play a crucial role in vivo as suggested by mutant enzymes introduced into embryos as mRNAs. The mutations in Gd that eliminate Na+ binding cause an apparent increase in activity, whereas mutations in Ea that abrogate Ca2+ binding result in complete loss of activity. A mutation in Ea predicted to introduce Na+ binding results in apparently increased activity with ventralization of the embryo, an effect not observed with wild-type Ea mRNA.

UR - http://www.scopus.com/inward/record.url?scp=0038176533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038176533&partnerID=8YFLogxK

U2 - 10.1074/jbc.M211820200

DO - 10.1074/jbc.M211820200

M3 - Article

C2 - 12493753

AN - SCOPUS:0038176533

VL - 278

SP - 11320

EP - 11330

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -