cd06461

Peptidase family M2, angiotensin converting enzyme (ACE)

CDD entry
Member databaseCDD
CDD typedomain
Short nameM2_ACE
SetGluZincin

Description

Peptidase family M2 angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc-dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor octapeptide angiotensin II, by removing two C-terminal amino acids. There are two forms of the enzyme in humans, the ubiquitous somatic ACE and the sperm-specific germinal ACE, both encoded by the same gene through transcription from alternative promoters. Somatic ACE has two tandem active sites with distinct catalytic properties, whereas germinal ACE, the function of which is largely unknown, has just a single active site. Recently, an ACE homolog, ACE2, has been identified in humans that differs from ACE; it preferentially removes carboxy-terminal hydrophobic or basic amino acids and appears to be important in cardiac function. ACE homologs (also known as members of the M2 gluzincin family) have been found in a wide variety of species, including those that neither have a cardiovascular system nor synthesize angiotensin. ACE is well-known as a key part of the renin-angiotensin system that regulates blood pressure and ACE inhibitors are important for the treatment of hypertension.
[5, 8, 7, 11, 10, 1, 12, 9, 2, 13, 6, 16, 3, 4, 14, 15]

References

1.Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. Dales NA, Gould AE, Brown JA, Calderwood EF, Guan B, Minor CA, Gavin JM, Hales P, Kaushik VK, Stewart M, Tummino PJ, Vickers CS, Ocain TD, Patane MA. J Am Chem Soc 124, 11852-3, (2002). PMID: 12358520

2.Evolutionary families of metallopeptidases. Rawlings ND, Barrett AJ. Meth. Enzymol. 248, 183-228, (1995). View articlePMID: 7674922

3.Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Li F, Li W, Farzan M, Harrison SC. Science 309, 1864-8, (2005). View articlePMID: 16166518

4.ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW. J. Biol. Chem. 279, 17996-8007, (2004). View articlePMID: 14754895

5.Angiotensin-converting enzyme and vascular remodeling. Heeneman S, Sluimer JC, Daemen MJ. Circ. Res. 101, 441-54, (2007). View articlePMID: 17761934

6.Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design. Corradi HR, Schwager SL, Nchinda AT, Sturrock ED, Acharya KR. J. Mol. Biol. 357, 964-74, (2006). View articlePMID: 16476442

7.Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system. Prokop JW, Petri V, Shimoyama ME, Watanabe IK, Casarini DE, Leeper TC, Bilinovich SM, Jacob HJ, Santos RA, Martins AS, Araujo FC, Reis FM, Milsted A. Gen Comp Endocrinol 215, 106-16, (2015). PMID: 25260253

8.The N domain of human angiotensin-I-converting enzyme: the role of N-glycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407. Anthony CS, Corradi HR, Schwager SL, Redelinghuys P, Georgiadis D, Dive V, Acharya KR, Sturrock ED. J. Biol. Chem. 285, 35685-93, (2010). View articlePMID: 20826823

9.Characterization of the first non-insect invertebrate functional angiotensin-converting enzyme (ACE): leech TtACE resembles the N-domain of mammalian ACE. Riviere G, Michaud A, Deloffre L, Vandenbulcke F, Levoye A, Breton C, Corvol P, Salzet M, Vieau D. Biochem J 382, 565-73, (2004). PMID: 15175004

10.Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P. J Biol Chem 277, 14838-43, (2002). PMID: 11815627

11.ACE2 orthologues in non-mammalian vertebrates (Danio, Gallus, Fugu, Tetraodon and Xenopus). Chou CF, Loh CB, Foo YK, Shen S, Fielding BC, Tan TH, Khan S, Wang Y, Lim SG, Hong W, Tan YJ, Fu J. Gene 377, 46-55, (2006). PMID: 16781089

12.Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril. Kim HM, Shin DR, Yoo OJ, Lee H, Lee JO. FEBS Lett. 538, 65-70, (2003). View articlePMID: 12633854

13.Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo. Savary K, Michaud A, Favier J, Larger E, Corvol P, Gasc JM. Blood 105, 103-10, (2005). PMID: 15367438

14.The emerging role of ACE2 in physiology and disease. Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD, Timens W, Turner AJ, Navis G, van Goor H. J. Pathol. 212, 1-11, (2007). View articlePMID: 17464936

15.Probing the basis of domain-dependent inhibition using novel ketone inhibitors of Angiotensin-converting enzyme. Watermeyer JM, Kroger WL, O'Neill HG, Sewell BT, Sturrock ED. Biochemistry 47, 5942-50, (2008). View articlePMID: 18457420

16.The structure of testis angiotensin-converting enzyme in complex with the C domain-specific inhibitor RXPA380. Corradi HR, Chitapi I, Sewell BT, Georgiadis D, Dive V, Sturrock ED, Acharya KR. Biochemistry 46, 5473-8, (2007). View articlePMID: 17439247

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