4aa2
Crystal structure of ANCE in complex with bradykinin potentiating peptide bCrystal structure of ANCE in complex with bradykinin potentiating peptide b
Structural highlights
Function[ACE_DROME] May be involved in the specific maturation or degradation of a number of bioactive peptides. May play a role in the contractions of the heart, gut and testes, and in spermatid differentiation.[1] [BNP_GLOBL] Blomhotin: inhibits the rabbit lung angiotensin-converting enzyme (ACE) with an IC(50) of 15 uM. Bradykinin-potentiating peptide A: causes no contraction of the rat gastric fundus smooth muscle even at high concentrations. Bradykinin-potentiating peptide B: inhibits the activity of the angiotensin-converting enzyme (ACE) by a preferential interaction with its C-domain. Also potentiates the hypotensive effects of bradykinin. Inhibits the rabbit lung ACE with an IC(50) of 1.1 uM. Bradykinin-potentiating peptide C: inhibits the activity of the angiotensin-converting enzyme (ACE) by interacting with the same potency to its C- and N-domains (PubMed:11994001). Inhibits the rabbit lung angiotensin-converting enzyme (ACE) with an IC(50) of 7.1 uM.[2] Leu3-blomhotin: inhibits the rabbit lung angiotensin-converting enzyme (ACE) with an IC(50) of 46 uM. Synthetic Leu3-blomhotin contracts the rat gastric fundus smooth muscle in a rapid and transient manner. Bradykinin-potentiating peptide Ahb1: potentiates the bradykinin in vivo. Bradykinin-potentiating peptide Ahb2: does not show any bradykinin-potentiating effects. C-type natriuretic peptide: exhibits hypotensive and vasodepressor activity. Acts by activating natriuretic receptors (NPR1 and/or NPR2 and/or NPR3) (By similarity). Publication Abstract from PubMedHuman somatic angiotensin-1 converting enzyme (ACE) is a zinc-dependent exopeptidase, that catalyses the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a C-terminal dipeptide. It is the principal component of the renin-angiotensin-aldosterone system that regulates blood pressure. Hence it is an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the structures of an ACE homologue from Drosophila melanogaster (AnCE; a proven structural model for the more complex human ACE) co-crystallized with mammalian peptide substrates (bradykinin, Thr(6) -bradykinin, angiotensin I and a snake venom peptide inhibitor, bradykinin-potentiating peptide-b). The structures determined at 2-A resolution illustrate that both angiotensin II (the cleaved product of angiotensin I by AnCE) and bradykinin-potentiating peptide-b bind in an analogous fashion at the active site of AnCE, but also exhibit significant differences. In addition, the binding of Arg-Pro-Pro, the cleavage product of bradykinin and Thr(6) - bradykinin, provides additional detail of the general peptide binding in AnCE. Thus the new structures of AnCE complexes presented here improves our understanding of the binding of peptides and the mechanism by which peptides inhibit this family of enzymes. DATABASE: The atomic coordinates and structure factors for AnCE-Ang II (code 4AA1), AnCE-BPPb (code 4AA2), AnCE-BK (code 4ASQ) and AnCE-Thr6-BK (code 4ASR) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/) STRUCTURED DIGITAL ABSTRACT: * AnCE cleaves Ang I by enzymatic study (View interaction) * Bradykinin and AnCE bind by x-ray crystallography (View interaction) * BPP and AnCE bind by x-ray crystallography (View interaction) * AnCE cleaves Bradykinin by enzymatic study (View interaction) * Ang II and AnCE bind by x-ray crystallography (View interaction). Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster.,Akif M, Masuyer G, Bingham RJ, Sturrock ED, Isaac RE, Acharya KR FEBS J. 2012 Oct 20. doi: 10.1111/febs.12038. PMID:23082758[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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