The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the two compounds binds in the canonic manner to the zinc ion and interacts with Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor was positioned in the hydrophobic part of the binding pocket, at van der Waals distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These structures may help in the design of better inhibitors of these widespread zinc-containing enzymes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2006.09.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cell-Free Carbonic Anhydrase IX mRNA in Urine as Biomarker for Urogenital Cancers: The Relationship Between Urinary Extracellular RNA and Tumor-Cell-Associated RNA.
Curr Issues Mol Biol
December 2024
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Gaetano Pieraccini 6, 51039 Florence, Italy.
Circulating tumor cells and cell-free nucleic acids are novel diagnostic, prognostic and predictive tools for non-invasive and cost-effective cancer detection in liquid biopsy. Carbonic anhydrase IX (CAIX) has been proposed as a biomarker in urogenital tumors and urine sediment. Our aim was to evaluate CAIX full-length percentage (CAIX FL%) in urine-cell-free RNA (cfRNA) and its relationship with tumor-cell-associated RNA (TC-RNA).
View Article and Find Full Text PDFPurpose: To evaluate the safety and efficacy of sublingual methazolamide in patients with open-angle glaucoma (OAG) and inform future trial design.
Methods: Fourteen participants (28 eyes) aged 50 to 90 years with bilateral OAG and intraocular pressure (IOP) between 18 and 35 mmHg after medication washout were included. Participants were randomized to receive either 25 mg or 50 mg of sublingual methazolamide once daily for one week, followed by twice-daily administration during the second week.
Assessing the Risk of Kidney Stone Development in Patients With Idiopathic Intracranial Hypertension Treated With Carbonic Anhydrase Inhibitors.
J Neuroophthalmol
December 2024
College of Medicine (JM, AGL), Texas A&M University, Houston, Texas; Department of Ophthalmology (SAA, OAD, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Ophthalmology (SAA), The University of Jordan, Amman, Jordan; Department of Ophthalmology (OAD), Hashemite University, Amman, Jordan; Department of Ophthalmology (AL, AGL), Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Background: The prevalence of idiopathic intracranial hypertension (IIH) is rising with the global obesity epidemic. Carbonic anhydrase inhibitors (CAIs), such as acetazolamide, have been shown to be effective in IIH but can also lead to kidney stone formation. This study evaluates the risk of kidney stone development in patients with IIH treated with CAIs.
View Article and Find Full Text PDFMetastasis of clear cell renal cell carcinoma to hyalinizing trabecular tumor of the thyroid: A case report.
Oncol Lett
March 2025
Department of Pathology, Beilun District People's Hospital of Ningbo City, Ningbo, Zhejiang 315000, P.R. China.
Renal cell carcinoma (RCC) is the most common malignancy that metastasizes to the thyroid; however, metastasis of RCC to a primary tumor of the thyroid is rare. The present study reports the case of RCC that had metastasized to the primary thyroid tumor; namely, a hyalinizing trabecular tumor (HTT). Notably, the RCC was resected 2 years prior.
View Article and Find Full Text PDFHippocampus carbonic anhydrase 1 via ERK pathway may be involved in depressive like behaviors.
J Affect Disord
December 2024
Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, 400016, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 400016, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address:
Major depressive disorder (MDD) is a destructive mental disease, yet the mechanism is still not clear. Carbonic anhydrase, an efficient catalyst for CO conversion to carbonate and protons, could affect many functions, such as memory formation recognition. Lately, we illustrated that carbonic anhydrase 1 (CAR1) knockout (CAR1) mice could lead to depressive-like behaviors, but the underlying molecular mechanism is unknown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!