PMID- 8557623
OWN - NLM
STAT- MEDLINE
DCOM- 19960226
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 2
DP  - 1996 Jan 12
TI  - Unexpected binding mode of the sulfonamide fluorophore 
      5-dimethylamino-1-naphthalene sulfonamide to human carbonic anhydrase II. 
      Implications for the development of a zinc biosensor.
PG  - 1003-7
AB  - The three-dimensional structure of human carbonic anhydrase II (CAII) complexed 
      with the sulfonamide fluorophore 5-dimethylamino-1-naphthalene sulfonamide 
      (dansylamide) has been determined to 2.1-A resolution by x-ray crystallographic 
      methods. Unlike other arylsulfonamide inhibitors of CAII, the naphthyl ring of 
      dansylamide binds in a hydrophobic pocket in the active site, making van der 
      Waals contacts with Val-121, Phe-131, Val-143, Leu-198, and Trp-209. 
      Interestingly, a conformational change of Leu-198 is required to accommodate 
      dansylamide binding, which rationalizes the enhanced dansylamide affinity 
      measured for certain Leu-198 variants (Nair, S. K., Krebs, J.F., Christianson, D. 
      W., and Fierke, C. A. (1995) Biochemistry 34, 3981-3989). Modeling studies 
      indicate that a second binding mode, in which the fused aromatic ring is rotated 
      out of the hydrophobic pocket, is sterically feasible. Both experimentally 
      observed and modeled binding modes have implications for new leads in the design 
      of avid CAII inhibitors. Finally, the structure of the CAII-dansylamide complex 
      has implications for its exploitation in zinc biosensor applications, and 
      possible routes toward the optimization of fluorophore design are considered on 
      the basis on this structure.
FAU - Nair, S K
AU  - Nair SK
AD  - Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, 
      USA.
FAU - Elbaum, D
AU  - Elbaum D
FAU - Christianson, D W
AU  - Christianson DW
LA  - eng
GR  - F32 CA62613/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Dansyl Compounds)
RN  - 0 (Fluorescent Dyes)
RN  - 1431-39-6 (5-dimethylaminonaphthalene-1-sulfonamide)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Carbonic Anhydrases/*metabolism
MH  - Crystallography, X-Ray
MH  - Dansyl Compounds/*metabolism
MH  - Fluorescent Dyes/metabolism
MH  - Humans
MH  - Protein Conformation
EDAT- 1996/01/12 00:00
MHDA- 1996/01/12 00:01
CRDT- 1996/01/12 00:00
PHST- 1996/01/12 00:00 [pubmed]
PHST- 1996/01/12 00:01 [medline]
PHST- 1996/01/12 00:00 [entrez]
AID - S0021-9258(18)95531-6 [pii]
AID - 10.1074/jbc.271.2.1003 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Jan 12;271(2):1003-7. doi: 10.1074/jbc.271.2.1003.