2C6N

Structure of human somatic angiontensin-I converting enzyme N domain with lisinopril

Summary for 2C6N

• Entry DOI: 10.2210/pdb2c6n/pdb
• Related: 2C6F
• Related PRD ID: PRD_000560
• Descriptor: ANGIOTENSIN-CONVERTING ENZYME, SOMATIC ISOFORM, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: hydrolase, angiotensin-i converting enzyme, n domain, zinc metallopeptidase, metalloprotease, angiotensin, lisinopril, carboxypeptidase, glycoprotein, metal-binding, phosphorylation, protease, transmembrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 144061.86

Authors

Corradi, H.R.,Schwager, S.L.U.,Nichinda, A.,Sturrock, E.D.,Acharya, K.R. (deposition date: 2005-11-10, release date: 2006-03-15, Last modification date: 2024-11-06)

Primary citation

Corradi, H.R.,Schwager, S.L.,Nchinda, A.T.,Sturrock, E.D.,Acharya, K.R.
Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design.
J. Mol. Biol., 357:964-974, 2006

PubMed Abstract: Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of "domain-specific" second-generation ACE inhibitors.

PubMed: 16476442
DOI: 10.1016/j.jmb.2006.01.048

Experimental method

X-RAY DIFFRACTION (3 Å)