6d1m | pdb_00006d1m

Design, synthesis, and X-ray of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects

Structural highlights

6d1m is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	FQY, GOL, ZN
Activity:	Carbonate dehydratase, with EC number 4.2.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.^[1] ^[2] ^[3] ^[4] ^[5]

Function

[CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.^[6] ^[7]

Publication Abstract from PubMed

A series of selenides bearing benzensulfonamide were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Potent inhibitory action, in the low nanomolar range, was detected against isoforms hCA II and VII, which are known to be involved in neuropathic pain modulation. These selenides showed on the other hand moderate inhibition against the cytosolic isoforms hCA I and transmembrane hCA IX. X-ray crystallographic data of two derivatives bound to hCA II allowed us to rationalize the excellent inhibitory data. In a mice model of neuropathic pain induced by oxaliplatin, some of the strong CA II/VII inhibitors induced a long lasting pain relieving effect.

Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects.,Angeli A, di Cesare Mannelli L, Lucarini E, Peat TS, Ghelardini C, Supuran CT Eur J Med Chem. 2018 Jun 25;154:210-219. doi: 10.1016/j.ejmech.2018.05.026. Epub , 2018 May 19. PMID:29803994^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE. Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. Am J Hum Genet. 1991 Nov;49(5):1082-90. PMID:1928091
↑ Roth DE, Venta PJ, Tashian RE, Sly WS. Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8. PMID:1542674
↑ Soda H, Yukizane S, Yoshida I, Koga Y, Aramaki S, Kato H. A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement. Hum Genet. 1996 Apr;97(4):435-7. PMID:8834238
↑ Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS. Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum Mutat. 1997;9(5):383-7. PMID:9143915 doi:<383::AID-HUMU1>3.0.CO;2-5 10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.0.CO;2-5
↑ Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004 Sep;24(3):272. PMID:15300855 doi:10.1002/humu.9266
↑ Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681
↑ Kim CY, Whittington DA, Chang JS, Liao J, May JA, Christianson DW. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. J Med Chem. 2002 Feb 14;45(4):888-93. PMID:11831900
↑ Angeli A, di Cesare Mannelli L, Lucarini E, Peat TS, Ghelardini C, Supuran CT. Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects. Eur J Med Chem. 2018 Jun 25;154:210-219. doi: 10.1016/j.ejmech.2018.05.026. Epub , 2018 May 19. PMID:29803994 doi:https://dx.doi.org/10.1016/j.ejmech.2018.05.026

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OCA

[1] Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE. Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. Am J Hum Genet. 1991 Nov;49(5):1082-90. PMID:1928091

[2] Roth DE, Venta PJ, Tashian RE, Sly WS. Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8. PMID:1542674

[3] Soda H, Yukizane S, Yoshida I, Koga Y, Aramaki S, Kato H. A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement. Hum Genet. 1996 Apr;97(4):435-7. PMID:8834238

[4] Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS. Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum Mutat. 1997;9(5):383-7. PMID:9143915 doi:<383::AID-HUMU1>3.0.CO;2-5 10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.0.CO;2-5

[5] Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004 Sep;24(3):272. PMID:15300855 doi:10.1002/humu.9266

[6] Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681

[7] Kim CY, Whittington DA, Chang JS, Liao J, May JA, Christianson DW. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. J Med Chem. 2002 Feb 14;45(4):888-93. PMID:11831900

[8] Angeli A, di Cesare Mannelli L, Lucarini E, Peat TS, Ghelardini C, Supuran CT. Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects. Eur J Med Chem. 2018 Jun 25;154:210-219. doi: 10.1016/j.ejmech.2018.05.026. Epub , 2018 May 19. PMID:29803994 doi:https://dx.doi.org/10.1016/j.ejmech.2018.05.026

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6d1m | pdb_00006d1m

Design, synthesis, and X-ray of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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