NMR studies of carbonic anhydrase-fluorinated benzenesulfonamide complexes

Journal Article · Tue May 02 00:00:00 EDT 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00435a049· OSTI ID:5443604

Dugad, L B; Cooley, C R; Gerig, J T ^[1]

---

1. Univ. of California, Santa Barbara (USA)

Fluorine NMR has been used to examine complexes formed by 2-fluoro-, 3-fluoro-, and 2,5-difluorobenzenesulfonamide and human carbonic anhydrases I and II. The results show that all three inhibitors form complexes with both isozymes that have 2:1 inhibitor/enzyme stoichiometry. The fluorine spectra observed for all inhibitor-isozyme combinations are consistent either with rapid rotation of the aromatic ring of the inhibitor in the complexes or with preferential binding of only one of the two possible conformations of the inhibitors that are isomeric by virtue of rotation about the C{sub 1}-C{sub 4} bond of the fluoro aromatic ring. Because ring rotation is slow in the case of the pentafluorobenzenesulfonamide-CA I complex, selective binding of rotamers is the explanation of these observations presently favored. A computer graphics study shows that formation of 2:1 complexes of CA I is feasible without appreciable distortion of the protein tertiary structure found in the crystalline state.

• OSTI ID: 5443604
• Journal Information: Biochemistry; (USA), Vol. 28:9; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ENZYME INHIBITORS
CROSS-LINKING
OXIDOREDUCTASES
SULFONAMIDES
NUCLEAR MAGNETIC RESONANCE
FLUORINATED AROMATIC HYDROCARBONS
FLUORINE
ISOENZYMES
AMIDES
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
AROMATICS
CHEMICAL REACTIONS
DRUGS
ELEMENTS
ENZYMES
HALOGENATED AROMATIC HYDROCARBONS
HALOGENS
MAGNETIC RESONANCE
NONMETALS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POLYMERIZATION
RESONANCE
550201* - Biochemistry- Tracer Techniques