ACE for all

A molecular perspective

Charlotte Harrison, K. Ravi Acharya

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 % amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level.
Original languageEnglish
Pages (from-to)195-210
JournalJournal of Cell Communication and Signaling
Volume8
Issue number3
Early online date16 Jul 2014
DOIs
Publication statusPublished - Sep 2014

Fingerprint

Insects
Enzymes
Angiotensin-Converting Enzyme Inhibitors
Genes
Pressure regulation
Genome
Physiological Phenomena
Anopheles gambiae
Blood pressure
Angiotensins
Peptidyl-Dipeptidase A
Renin-Angiotensin System
Cardiovascular System
Aldosterone
Renin
Zinc
Amino Acid Sequence
Catalytic Domain
Crystal structure
Blood Pressure

Cite this

ACE for all : A molecular perspective. / Harrison, Charlotte; Acharya, K. Ravi.

In: Journal of Cell Communication and Signaling, Vol. 8, No. 3, 09.2014, p. 195-210.

Research output: Contribution to journalArticle

@article{1d43158ffb474b43a41864d30fcb1bb1,
title = "ACE for all: A molecular perspective",
abstract = "Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 {\%} amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level.",
author = "Charlotte Harrison and Acharya, {K. Ravi}",
year = "2014",
month = "9",
doi = "10.1007/s12079-014-0236-8",
language = "English",
volume = "8",
pages = "195--210",
journal = "Journal of Cell Communication and Signaling",
issn = "1873-9601",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - ACE for all

T2 - A molecular perspective

AU - Harrison, Charlotte

AU - Acharya, K. Ravi

PY - 2014/9

Y1 - 2014/9

N2 - Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 % amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level.

AB - Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 % amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level.

UR - http://www.scopus.com/inward/record.url?scp=84904232632&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1007/s12079-014-0236-8

U2 - 10.1007/s12079-014-0236-8

DO - 10.1007/s12079-014-0236-8

M3 - Article

VL - 8

SP - 195

EP - 210

JO - Journal of Cell Communication and Signaling

JF - Journal of Cell Communication and Signaling

SN - 1873-9601

IS - 3

ER -