ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.

The Journal of Biological Chemistry
Paul TowlerMichael W Pantoliano


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 f...Continue Reading


May 29, 1991·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·J R Knowles
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M R EhlersJ F Riordan
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·F SoubrierP Corvol
Oct 28, 1988·Science·J Kraut
Apr 20, 1967·Biochemical and Biophysical Research Communications·I Schechter, A Berger
Oct 23, 1984·Biochemistry·R Shapiro, J F Riordan
Nov 20, 1980·Nature·A A PatchettC A Stone
Feb 28, 1984·Biochemistry·M W PantolianoJ F Riordan
Jan 1, 1995·Methods in Enzymology·N D Rawlings, A J Barrett
Jun 7, 1994·Biochemistry·M GersteinC Chothia
Jan 1, 1996·Methods in Enzymology·D G HigginsT J Gibson
Dec 1, 1995·Proteins·D Frishman, P Argos
Aug 1, 1996·Nature Structural Biology·F GramsW Stöcker
Jan 1, 1997·Methods : a Companion to Methods in Enzymology·T N MarionD M Tillman
Sep 2, 1998·Nucleic Acids Research·M Gerstein, W Krebs
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Nov 18, 1998·Current Opinion in Structural Biology·J P Abrahams, R A De Graaff
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·C K BrownD W Rodgers
Jan 30, 2002·The Journal of Biological Chemistry·Chad VickersPeter Tummino
Apr 5, 2002·Trends in Pharmacological Sciences·Anthony J Turner, Nigel M Hooper
Jun 21, 2002·Nature·Michael A CrackowerJosef M Penninger
Oct 3, 2002·Journal of the American Chemical Society·Natalie A DalesMichael A Patane
Jan 24, 2003·Nature·Ramanathan NateshK Ravi Acharya
Jan 25, 2003·The Biochemical Journal·Kerry GordonEdward D Sturrock
Apr 15, 2003·Trends in Cardiovascular Medicine·Gavin Y OuditJosef M Penninger
Apr 18, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ursula DanilczykJosef M Penninger
Jul 3, 2003·Nature Reviews. Drug Discovery·Simon J Teague
Oct 24, 2003·Acta Crystallographica. Section D, Biological Crystallography·G BricogneW Paciorek
Dec 4, 2003·Biochemical and Biophysical Research Communications·Xiaodong XiaoDimiter S Dimitrov
Jan 1, 1997·Methods in Enzymology·Jorge Navaza, Pedro Saludjian

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