INFLUENCE OF METAL SUBSTITUTION ON VITAMIN-B12 BINDING TO HUMAN INTRINSIC-FACTOR AND TRANSCOBALAMIN-I AND TRANSCOBALAMIN-II

被引:8
作者
ELSENHANS, B [1 ]
ROSENBERG, IH [1 ]
机构
[1] UNIV CHICAGO, DEPT MED, BASIC MED SCI SECT, CHICAGO, IL 60637 USA
关键词
D O I
10.1021/bi00300a004
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
Metal-free, Zn, Cu, and Rh analogues of vitamin B12 were synthesized to further characterize structural requirements for the binding to human intrinsic factor, transcobalamin I and transcobalamin II. Binding affinities of the various analogues were studied by competition against cyano[57Co]cobalamin. When albumin-coated charcoal was used for the separation of free and bound corrinoids, the relative 50% inhibition indexes were determined. The influence of metal substitution was similar among the 3 binding proteins. For analogues with a strong coordinative linkage between the heterocyclic base and the central metal ion, similar to that with Co (e.g., zincobalamin and cyanorhodibalamin), the indexes range from 0.65-2.35 for all 3 binding proteins. Analogues in which corrdination is impossible (hydrogenobalamin and dicyanorhodibalamin) exhibit markedly reduced binding with indexes between 10-160. Cupribalamin shows 50% inhibition indexes ranging from 2.3-5.0, thus suggesting a weak coordinative bond between the Cu and the 5.6-dimethylbenzimidazole moiety. The importance of the coordinative linkage between the central metal ion and the nucleotide moiety for optimal recognition by vitamin B12 binding proteins is emphasized.
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页码:805 / 808
页数:4
相关论文
共 22 条
[11]  
KOPPENHAGEN VB, 1973, J BIOL CHEM, V248, P7999
[12]  
KOPPENHAGEN VB, 1974, J BIOL CHEM, V249, P6532
[13]  
KOPPENHAGEN VB, 1981, VITAMIN B12
[14]  
LIEN EL, 1974, J BIOL CHEM, V249, P890
[15]   MECHANISM OF COBALAMIN BINDING TO HOG INTRINSIC-FACTOR [J].
LIEN, EL ;
ELLENBOGEN, L ;
LAW, PY ;
WOOD, JM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1973, 55 (03) :730-735
[16]  
PRATT JM, 1972, INORGANIC CHEM VITAM, P135
[17]  
RENZ P, 1971, METHODS ENZYMOL C, V18, P85
[18]   SEPARATION OF VITAMIN B12-BINDING PROTEINS OF SERUM GASTRIC JUICE AND SALIVA BY RAPID DEAE CELLULOSE CHROMATOGRAPHY [J].
RETIEF, FP ;
GOTTLIEB, CW ;
KOCHWA, S ;
PRATT, PW ;
HERBERT, V .
BLOOD-THE JOURNAL OF HEMATOLOGY, 1967, 29 (4P1) :501-&
[20]   KINETICS OF INTRINSIC FACTOR VITAMIN-B12 BINDING [J].
WAGSTAFF, M ;
BROUGHTON, A ;
JONES, FR .
BIOCHIMICA ET BIOPHYSICA ACTA, 1973, 320 (02) :406-415