4AA2

Crystal structure of ANCE in complex with bradykinin potentiating peptide b

Summary for 4AA2

• Entry DOI: 10.2210/pdb4aa2/pdb
• Related: 1J36 1J37 1J38 2X8Y 2X8Z 2X90 2X91 2X92 2X93 2X94 2X95 2X96 2X97 2XHM 3ZQZ 4AA1
• Descriptor: ANGIOTENSIN-CONVERTING ENZYME, BRADYKININ-POTENTIATING PEPTIDE B, beta-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: hydrolase-peptide complex, hydrolase, substrate binding, inhibitor, hydrolase/peptide
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY); More
• Total number of polymer chains: 2
• Total formula weight: 71935.84

Authors

Isaac, R.E.,Akif, M.,Schwager, S.L.U.,Masuyer, G.,Sturrock, E.D.,Acharya, K.R. (deposition date: 2011-11-30, release date: 2012-10-31, Last modification date: 2024-11-20)

Primary citation

Akif, M.,Masuyer, G.,Bingham, R.J.,Sturrock, E.D.,Isaac, R.E.,Acharya, K.R.
Structural Basis of Peptide Recognition by the Angiotensin-I Converting Enzyme Homologue Ance from Drosophila Melanogaster
FEBS J., 279:4525-, 2012

PubMed Abstract: Human 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-Å 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.

PubMed: 23082758
DOI: 10.1111/FEBS.12038

Experimental method

X-RAY DIFFRACTION (1.99 Å)