Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine

被引:231
作者
Briganti, F
Mangani, S
Orioli, P
Scozzafava, A
Vernaglione, G
Supuran, CT
机构
[1] UNIV FLORENCE,DIPARTIMENTO CHIM,LAB CHIM INORGAN & BIOINORGAN,I-50121 FLORENCE,ITALY
[2] UNIV SIENA,DIPARTIMENTO CHIM,I-53100 SIENA,ITALY
关键词
D O I
10.1021/bi970760v
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The interaction of native and Co(II)-substituted isozymes I and II of carbonic anhydrase (CA) with histamine, a well-known activator, was investigated kinetically, spectroscopically, and X-ray crystallographically. This activator is of the noncompetitive type with 4-nitrophenyl acetate and CO2, as substrates for both HCA I and HCA II. The electronic spectrum of the adduct of Co(II)-HCA II with histamine is similar to the spectrum of the Co(II)-HCA II-phenol adduct, being only slightly different from that of the uncomplexed enzyme. This is the first spectroscopic evidence that the activator molecule binds within the active site, but not directly to the metal ion. X-ray crystallographic data for the adduct of HCA II with histamine showed that the activator molecule is bound at the entrance of the active site cavity in a position where it may actively participate in shuttling protons between the active site and the hulk solvent. The role of the activators and the reported X-ray crystal structure of the HCA II-histamine adduct has prompted us to reexamine the X-ray structures of the different CA isozymes in elder to find a structural basis accounting for their large differences in catalytic rate. A tentative explanation is proposed on the basis of possible pathways of proton transfer, which constitute the rate-limiting step in the catalytic reaction.
引用
收藏
页码:10384 / 10392
页数:9
相关论文
共 85 条
  • [61] PUSCAS I, 1994, CARBONIC ANHYDRASE M, P147
  • [62] IMPROVED FOURIER COEFFICIENTS FOR MAPS USING PHASES FROM PARTIAL STRUCTURES WITH ERRORS
    READ, RJ
    [J]. ACTA CRYSTALLOGRAPHICA SECTION A, 1986, 42 : 140 - 149
  • [63] Roughton F. J. W., 1943, HARVEY LECT, V39, P96
  • [64] ROWLETT RS, 1991, J BIOL CHEM, V266, P933
  • [65] SANYAL G, 1982, MOL PHARMACOL, V22, P211
  • [66] ACTIVATION OF CARBONIC ANHYDRASE-III BY PHOSPHATE
    SHELTON, JB
    CHEGWIDDEN, WR
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 1988, 16 (05) : 853 - 854
  • [67] THE CATALYTIC MECHANISM OF CARBONIC-ANHYDRASE - IMPLICATIONS OF A RATE-LIMITING PROTOLYSIS OF WATER
    SILVERMAN, DN
    LINDSKOG, S
    [J]. ACCOUNTS OF CHEMICAL RESEARCH, 1988, 21 (01) : 30 - 36
  • [68] PHENOL, A COMPETITIVE INHIBITOR OF CO2 HYDRATION CATALYZED BY CARBONIC-ANHYDRASE
    SIMONSSON, I
    JONSSON, BH
    LINDSKOG, S
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1982, 108 (04) : 1406 - 1412
  • [69] POSITIONS OF HIS-64 AND A BOUND WATER IN HUMAN CARBONIC-ANHYDRASE-II UPON BINDING 3 STRUCTURALLY RELATED INHIBITORS
    SMITH, GM
    ALEXANDER, RS
    CHRISTIANSON, DW
    MCKEEVER, BM
    PONTICELLO, GS
    SPRINGER, JP
    RANDALL, WC
    BALDWIN, JJ
    HABECKER, CN
    [J]. PROTEIN SCIENCE, 1994, 3 (01) : 118 - 125
  • [70] Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-angstrom resolution
    Stams, T
    Nair, SK
    Okuyama, T
    Waheed, A
    Sly, WS
    Christianson, DW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) : 13589 - 13594