First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.

2x93

From Proteopedia

Jump to: navigation, search


2x93, resolution 1.98Å ()
Ligands: , , , , ,
Activity: Peptidyl-dipeptidase A, with EC number 3.4.15.1
Related: 1j38, 1j36, 1j37, 2x94, 2x8z, 2x8y, 2x91, 2x95, 2x92, 2x96, 2x97, 2x90


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

CRYSTAL STRUCTURE OF ANCE-TRANDOLAPRILAT COMPLEX

Publication Abstract from PubMed

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE.

High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs., Akif M, Georgiadis D, Mahajan A, Dive V, Sturrock ED, Isaac RE, Acharya KR, J Mol Biol. 2010 Jul 16;400(3):502-17. Epub 2010 May 19. PMID:20488190

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2x93 is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

See Also

Reference

  • Akif M, Georgiadis D, Mahajan A, Dive V, Sturrock ED, Isaac RE, Acharya KR. High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs. J Mol Biol. 2010 Jul 16;400(3):502-17. Epub 2010 May 19. PMID:20488190 doi:10.1016/j.jmb.2010.05.024

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools