1R42

Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2)

Summary for 1R42

• Entry DOI: 10.2210/pdb1r42/pdb
• Related: 1R4L
• Descriptor: angiotensin I converting enzyme 2, disordered segment of collectrin homology domain, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: zinc metallopeptidase domain, collectrin homology domain, native or open conformation, chloride ion binding site, zinc binding site, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 76772.45

Authors

Towler, P.,Staker, B.,Prasad, S.G.,Menon, S.,Ryan, D.,Tang, J.,Parsons, T.,Fisher, M.,Williams, D.,Dales, N.A.,Patane, M.A.,Pantoliano, M.W. (deposition date: 2003-10-07, release date: 2004-02-03, Last modification date: 2024-10-16)

Primary citation

Towler, P.,Staker, B.,Prasad, S.G.,Menon, S.,Tang, J.,Parsons, T.,Ryan, D.,Fisher, M.,Williams, D.,Dales, N.A.,Patane, M.A.,Pantoliano, M.W.
ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.
J.Biol.Chem., 279:17996-18007, 2004

PubMed Abstract: The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence. ACE2 has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). To gain further insights into this enzyme, the first crystal structures of the native and inhibitor-bound forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-A resolution, respectively. Comparison of these structures revealed a large inhibitor-dependent hinge-bending movement of one catalytic subdomain relative to the other ( approximately 16 degrees ) that brings important residues into position for catalysis. The potent inhibitor MLN-4760 ((S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol4-yl]-ethylamino]-4-methylpentanoic acid) makes key binding interactions within the active site and offers insights regarding the action of residues involved in catalysis and substrate specificity. A few active site residue substitutions in ACE2 relative to ACE appear to eliminate the S(2)' substrate-binding subsite and account for the observed reactivity change from the peptidyl dipeptidase activity of ACE to the carboxypeptidase activity of ACE2.

PubMed: 14754895
DOI: 10.1074/jbc.M311191200

Experimental method

X-RAY DIFFRACTION (2.2 Å)