Angiotensin-Converting Enzyme: Difference between revisions

{{STRUCTURE_1o8a| right| PDB=1o8a  | SCENE= |CAPTION= Crystal Structure of Human tACE, [[1o8a]] }}

[[Angiotensin-Converting Enzyme]] (ACE) is both an exopeptidase and endopeptindase first discovered by Skeggs et al. in 1956. <ref>Skeggs, L. T., Dorer, F. E., Kahn, J. R., Lentz, K. E., Levin, M. (1981) Experimental renal hypertension: the discovery of the Renin-Angiotensin system. Soffer, R. eds. Biochemical Regulation of Blood Pressure ,3-38 John Wiley & Sons, Inc. Hoboken.</ref> ACE is a zinc- and chloride-dependent metallopeptidase that is responsible for the metabolism of key biologically active peptides, namely Angiotensin I and [[Bradykinin]]. These two peptides play a critical role in maintaining appropriate blood pressure in the human body along with a host of other homeostatic circulatory functions. Due to its critical role in the [http://en.wikipedia.org/wiki/RAAS Renin-Angiotensin-Aldosterone System (RAAS)], ACE has been targeted by a number of pharmaceutical compounds to treat [http://en.wikipedia.org/wiki/Hypertension hypertension], [http://en.wikipedia.org/wiki/Diabetic_neuropathy diabetic nephropathy], and [http://en.wikipedia.org/wiki/Renal_failure renal failure]. <ref>PMID:10780101</ref>

==Biological Role==

ACE is a Zn and Chloride dependent type-1 membrane protein (N-terminal regions are outside the cell). Two types of Angiotensin-converting enzyme exist, ACE1 and ACE2, although the most focus has been on ACE1 which has been attributed with receptor-mediated effects like vasoconstriction, inflammation and cell growth/proliferation. <ref name="Ferrario">PMID:17083068</ref> The Renin-Angiotensin System (RAS) is a major regulator of blood pressure in the human body. [[Renin]] is an enzyme produced by the liver which cleaves Angiotensinogen into Angiotensin I Angiotensin Ihas the sequence, DRVTIHPFHL, and does not appear to have any biological activity. Angiotensin 1 is converted into Angiotensin II via the removal of the two C-terminal residues by ACE, yielding the active peptide: DRVTIHPF. <ref>PMID:12752436</ref>  

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!  colspan="2" align="center"| Selected AT1 and AT2 Receptor-Mediated Effects of Angiotensin II. <ref name="Weir"/><ref name="Ferrario"/>