9qam

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m (Protected "9qam" [edit=sysop:move=sysop])
Current revision (07:42, 12 November 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9qam is ON HOLD until Paper Publication
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==Human angiotensin-1 converting enzyme C-domain in complex with ciprofloxacin==
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<StructureSection load='9qam' size='340' side='right'caption='[[9qam]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9qam]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QAM FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AH2:(2~{R},3~{S},4~{R},5~{R})-2-(hydroxymethyl)oxane-3,4,5-triol'>AH2</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CPF:1-CYCLOPROPYL-6-FLUORO-4-OXO-7-PIPERAZIN-1-YL-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC+ACID'>CPF</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NXA:N-CARBOXYALANINE'>NXA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9qam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qam OCA], [https://pdbe.org/9qam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qam RCSB], [https://www.ebi.ac.uk/pdbsum/9qam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qam ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ACE_HUMAN ACE_HUMAN] Genetic variations in ACE may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:[https://omim.org/entry/267430 267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref> Genetic variations in ACE are associated with susceptibility to microvascular complications of diabetes type 3 (MVCD3) [MIM:[https://omim.org/entry/612624 612624]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in ACE are a cause of susceptibility to intracerebral hemorrhage (ICH) [MIM:[https://omim.org/entry/614519 614519]. A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.<ref>PMID:15277638</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ACE_HUMAN ACE_HUMAN] Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human somatic angiotensin I-converting enzyme is a key zinc metallopeptidase in cardiovascular regulation that hydrolyzes angiotensin peptides (Ang I, Ang II), as well as other vasoactive peptides, including kinins (e.g., bradykinin), substance P, the acetylated tetrapeptide Ac-Ser-Asp-Lys-Pro, and the amyloid ss-peptide. Because of its enzymatic promiscuity, ACE and its substrates and products affect many physiological processes, including blood pressure control, hemopoiesis, reproduction, renal development/function, fibrosis, and immune response. ACE inhibitors are among the most important therapeutic agents available today for the treatment of hypertension, heart failure, coronary artery disease, renal insufficiency, and general atherosclerosis. However, they need much improvement because of the side effects seen in patients with long-term treatment due to nonselective inhibition of the N- and C-domains of ACE (referred to as nACE and cACE, respectively). Here, we report that ACE activity can be inhibited by ciprofloxacin, a potent fluoroquinolone antibiotic (IC(50) 202.7/K (i) 33.8 muM for cACE). In addition, the high-resolution crystal structure of cACE in complex with ciprofloxacin reveals that it binds at an exosite away from the active site pocket, overlapping the position of a potential allosteric site with a different binding mode. The detailed structural information reported here will provide a useful scaffold for the design of future potent allosteric inhibitors.
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Authors: Gregory, K.S., Acharya, K.R.
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Ciprofloxacin Inhibits Angiotensin I‑Converting Enzyme (ACE) Activity by Binding at the Exosite, Distal to the Catalytic Pocket.,Gregory KS, Ramasamy V, Sturrock ED, Acharya KR ACS Bio Med Chem Au. 2025 Jun 10;5(5):852-859. doi: , 10.1021/acsbiomedchemau.5c00089. eCollection 2025 Oct 15. PMID:41112194<ref>PMID:41112194</ref>
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Description: Human angiotensin-1 converting enzyme C-domain in complex with ciprofloxacin
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Acharya, K.R]]
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<div class="pdbe-citations 9qam" style="background-color:#fffaf0;"></div>
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[[Category: Gregory, K.S]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Acharya KR]]
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[[Category: Gregory KS]]

Current revision

Human angiotensin-1 converting enzyme C-domain in complex with ciprofloxacin

PDB ID 9qam

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