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.
1r42
From Proteopedia
| 1r42, resolution 2.20Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Sites: | , , , and | ||||||||
| Ligands: | , , | ||||||||
| Non-Standard Residues: | |||||||||
| Gene: | ACE2 (Homo sapiens) | ||||||||
| Related: | 1r4l | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2)
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.
ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis., Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW, J Biol Chem. 2004 Apr 23;279(17):17996-8007. Epub 2004 Jan 30. PMID:14754895
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1R42 is a 5 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
See Angiotensin-Converting Enzyme for additional structural information.
Reference
- Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem. 2004 Apr 23;279(17):17996-8007. Epub 2004 Jan 30. PMID:14754895 doi:10.1074/jbc.M311191200
Page seeded by OCA on Wed Feb 18 06:04:30 2009
Categories: Homo sapiens | Dales, N A. | Fisher, M. | Menon, S. | Pantoliano, M W. | Parsons, T. | Patane, M A. | Prasad, S G. | Ryan, D. | Staker, B. | Tang, J. | Towler, P. | Williams, D. | Chloride ion binding site | Collectrin homology domain | Native or open conformation | Zinc binding site | Zinc metallopeptidase domain
