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Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme.

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Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme. / Coates, David; Isaac, R. Elwyn; Cotton, Joel et al.
In: Biochemistry, Vol. 39, No. 30, 08.2000, p. 8963-8969.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Coates, D, Isaac, RE, Cotton, J, Siviter, RJ, Williams, TA, Shirras, AD, Corvol, P & Dive, V 2000, 'Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme.', Biochemistry, vol. 39, no. 30, pp. 8963-8969. https://doi.org/10.1021/bi000593q

APA

Coates, D., Isaac, R. E., Cotton, J., Siviter, R. J., Williams, T. A., Shirras, A. D., Corvol, P., & Dive, V. (2000). Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme. Biochemistry, 39(30), 8963-8969. https://doi.org/10.1021/bi000593q

Vancouver

Coates D, Isaac RE, Cotton J, Siviter RJ, Williams TA, Shirras AD et al. Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme. Biochemistry. 2000 Aug;39(30):8963-8969. doi: 10.1021/bi000593q

Author

Coates, David ; Isaac, R. Elwyn ; Cotton, Joel et al. / Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme. In: Biochemistry. 2000 ; Vol. 39, No. 30. pp. 8963-8969.

Bibtex

@article{fee1b603bbe34707a84018b1346cfeda,
title = "Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme.",
abstract = "Human somatic angiotensin I-converting enzyme (sACE) has two active sites present in two homologous protein domains, resulting from a tandem gene duplication. It has been proposed that the N- and C-terminal active sites can have specific in vivo roles. In Drosophila melanogaster, Ance and Acer code for two ACE-like single-domain proteins, also predicted to have distinct physiological roles. We have investigated the relationship of Ance and Acer to the N- and C-domains of human sACE by genomic sequence analysis and by using domain-selective inhibitors, including RXP 407, a selective inhibitor of the human N-domain. These phosphinic peptides were potent inhibitors of Acer, but not of Ance. We conclude that the active sites of the N-domain and of Acer share structural features that permit the binding of the unusual RXP407 inhibitor and the hydrolysis of a broader range of peptide structures. In comparison, Ance, like the human C-domain of ACE, displays greater inhibitor selectivity. From the analysis of the published sequence of the Adh region of Drosophila chromosome 2, which carries Ance, Acer, and four additional ACE-like genes, we also suggest that this functional conservation is reflected in an ancestral gene structure identifiable in both protostome and deuterostome lineages and that the duplication seen in vertebrate genomes predates the divergence of these lineages. The conservation of ACE enzymes with distinct active sites in the evolution of both vertebrate and invertebrate species provides further evidence that these two kinds of active sites have different physiological functions.",
author = "David Coates and Isaac, {R. Elwyn} and Joel Cotton and Siviter, {Richard J.} and Williams, {Tracy A.} and Shirras, {Alan D.} and Pierre Corvol and Vincent Dive",
year = "2000",
month = aug,
doi = "10.1021/bi000593q",
language = "English",
volume = "39",
pages = "8963--8969",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "30",

}

RIS

TY - JOUR

T1 - Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme.

AU - Coates, David

AU - Isaac, R. Elwyn

AU - Cotton, Joel

AU - Siviter, Richard J.

AU - Williams, Tracy A.

AU - Shirras, Alan D.

AU - Corvol, Pierre

AU - Dive, Vincent

PY - 2000/8

Y1 - 2000/8

N2 - Human somatic angiotensin I-converting enzyme (sACE) has two active sites present in two homologous protein domains, resulting from a tandem gene duplication. It has been proposed that the N- and C-terminal active sites can have specific in vivo roles. In Drosophila melanogaster, Ance and Acer code for two ACE-like single-domain proteins, also predicted to have distinct physiological roles. We have investigated the relationship of Ance and Acer to the N- and C-domains of human sACE by genomic sequence analysis and by using domain-selective inhibitors, including RXP 407, a selective inhibitor of the human N-domain. These phosphinic peptides were potent inhibitors of Acer, but not of Ance. We conclude that the active sites of the N-domain and of Acer share structural features that permit the binding of the unusual RXP407 inhibitor and the hydrolysis of a broader range of peptide structures. In comparison, Ance, like the human C-domain of ACE, displays greater inhibitor selectivity. From the analysis of the published sequence of the Adh region of Drosophila chromosome 2, which carries Ance, Acer, and four additional ACE-like genes, we also suggest that this functional conservation is reflected in an ancestral gene structure identifiable in both protostome and deuterostome lineages and that the duplication seen in vertebrate genomes predates the divergence of these lineages. The conservation of ACE enzymes with distinct active sites in the evolution of both vertebrate and invertebrate species provides further evidence that these two kinds of active sites have different physiological functions.

AB - Human somatic angiotensin I-converting enzyme (sACE) has two active sites present in two homologous protein domains, resulting from a tandem gene duplication. It has been proposed that the N- and C-terminal active sites can have specific in vivo roles. In Drosophila melanogaster, Ance and Acer code for two ACE-like single-domain proteins, also predicted to have distinct physiological roles. We have investigated the relationship of Ance and Acer to the N- and C-domains of human sACE by genomic sequence analysis and by using domain-selective inhibitors, including RXP 407, a selective inhibitor of the human N-domain. These phosphinic peptides were potent inhibitors of Acer, but not of Ance. We conclude that the active sites of the N-domain and of Acer share structural features that permit the binding of the unusual RXP407 inhibitor and the hydrolysis of a broader range of peptide structures. In comparison, Ance, like the human C-domain of ACE, displays greater inhibitor selectivity. From the analysis of the published sequence of the Adh region of Drosophila chromosome 2, which carries Ance, Acer, and four additional ACE-like genes, we also suggest that this functional conservation is reflected in an ancestral gene structure identifiable in both protostome and deuterostome lineages and that the duplication seen in vertebrate genomes predates the divergence of these lineages. The conservation of ACE enzymes with distinct active sites in the evolution of both vertebrate and invertebrate species provides further evidence that these two kinds of active sites have different physiological functions.

U2 - 10.1021/bi000593q

DO - 10.1021/bi000593q

M3 - Journal article

VL - 39

SP - 8963

EP - 8969

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 30

ER -