8aae | pdb_00008aae
CAII in complex with para-carboran-propylsulfonamid
Structural highlights
DiseaseCAH2_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] FunctionCAH2_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 PubMedAmong non-covalent interactions, B-Hcdots, three dots, centeredpi and C-Hcdots, three dots, centeredpi hydrogen bonding is rather weak and less studied. Nevertheless, since both can affect the energetics of protein-ligand binding, their understanding is an important prerequisite for reliable predictions of affinities. Through a combination of high-resolution X-ray crystallography and quantum-chemical calculations on carbonic anhydrase II/carborane-based inhibitor systems, this paper provides the first example of B-Hcdots, three dots, centeredpi hydrogen bonding in a protein-ligand complex. It shows that the B-Hcdots, three dots, centeredpi interaction is stabilized by dispersion, followed by electrostatics. Furthermore, it demonstrates that the similar C-Hcdots, three dots, centeredpi interaction is twice as strong, with a slightly smaller contribution of dispersion and a slightly higher contribution of electrostatics. Such a detailed insight will facilitate the rational design of future protein ligands, controlling these types of non-covalent interactions. B-Hcdots, three dots, centeredpi and C-Hcdots, three dots, centeredpi interactions in protein-ligand complexes: carbonic anhydrase II inhibition by carborane sulfonamides.,Fanfrlik J, Brynda J, Kugler M, Lepsik M, Pospisilova K, Holub J, Hnyk D, Nekvinda J, Gruner B, Rezacova P Phys Chem Chem Phys. 2023 Jan 18;25(3):1728-1733. doi: 10.1039/d2cp04673c. PMID:36594655[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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