9GBN
Human Angiotensin-1 converting enzyme C-domain in complex with a diprolyl inhibitor- SG15
This is a non-PDB format compatible entry.
Summary for 9GBN
| Entry DOI | 10.2210/pdb9gbn/pdb |
| Descriptor | Angiotensin-converting enzyme, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total) |
| Functional Keywords | inhibitor, complex, protease, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 71205.34 |
| Authors | |
| Primary citation | Gregory, K.S.,Cozier, G.E.,Fienberg, S.,Chibale, K.,Sturrock, E.D.,Acharya, K.R. Molecular basis of human angiotensin-1 converting enzyme inhibition by a series of diprolyl-derived compounds. Febs J., 2025 Cited by PubMed Abstract: Angiotensin-1-converting enzyme (ACE) is a zinc-dependent carboxypeptidase of therapeutic interest for the treatment of hypertension, inflammation and fibrosis. It consists of two homologous N and C catalytic domains, nACE and cACE, respectively. Unfortunately, the current clinically available ACE inhibitors produce undesirable side effects due to the nonselective inhibition of these domains. Through structure-based drug design, we previously identified a series of diprolyl-derived inhibitors (SG3, SG15, SG16, SG17 and SG18) in an attempt to specifically target nACE. Only one compound, SG16, possessed significant nACEselectivity. The previously determined 16-nACE crystal structure (nACE:SG16) suggested interactions with Tyr369 (Phe381 in cACE) are responsible for this selectivity. To better understand the molecular basis for the lack of selectivity in the remaining compounds, we have cocrystallised nACE in complex with SG3, SG15, SG17 and SG18 and cACE in complex with SG3, SG15, SG16 and SG18 and determined their structures at high resolution. Apart from the catalytic residues, these structures further highlight the importance of residues distal to the active site that may play an important role in the design of domain-selective inhibitors of ACE. PubMed: 39763019DOI: 10.1111/febs.17384 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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