THEORETICAL EVALUATION OF CONFORMATIONAL PREFERENCES OF NAD+ AND NADH - AN APPROACH TO UNDERSTANDING THE STEREOSPECIFICITY OF NAD+ NADH-DEPENDENT DEHYDROGENASES

被引:94
作者
WU, YD
HOUK, KN
机构
[1] Contribution from the Department of Chemistry and Biochemistry, University of California, Los Angeles
关键词
D O I
10.1021/ja00007a002
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Potential energy surfaces for rotations of ribose about the nicotinamide N-C bonds in NAD+ and NADH have been evaluated from ab initio molecular orbital calculations with the 3-21G and 6-31G* basis sets. In the optimal conformation of NAD+ the glycosidic C-O bond is near the plane of the nicotinamide ring. By contrast, the lowest energy conformer of NADH has the glycosidic C-O bond nearly perpendicular to the dihydronicotinamide ring. The redox potential of the NAD+/NADH couple is a function of the ribose orientation. There is boat-like puckering of the 1,4-dihydropyridine ring, and the direction of the puckering is anti to the glycosidic bond. The geometry of the transition structure for hydride transfer is similar to that of NADH. When NADH is in the anti conformation, the transfer of the pro-R hydrogen is preferred, and when NADH is in the syn conformation, the transfer of the pro-S hydrogen is preferred.
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页码:2353 / 2358
页数:6
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共 88 条
  • [81] WHITE JL, 1976, J MOL BIOL, V102, P759, DOI 10.1016/0022-2836(76)90290-4
  • [82] WILKINSON KD, 1979, J BIOL CHEM, V254, P2567
  • [83] Wu Y., UNPUB
  • [84] TRANSITION STRUCTURES FOR HYDRIDE TRANSFERS
    WU, YD
    HOUK, KN
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (03) : 906 - 908
  • [85] REDUCTION BY A MODEL OF NAD(P)H .36. 1ST AND DIRECT EVIDENCE FOR THE MULTISTEP MECHANISM
    YASUI, S
    NAKAMURA, K
    OHNO, A
    OKA, S
    [J]. BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1982, 55 (01) : 196 - 199
  • [86] STEREOSPECIFICITY FOR NICOTINAMIDE NUCLEOTIDES IN ENZYMATIC AND CHEMICAL HYDRIDE TRANSFER-REACTIONS
    YOU, KS
    [J]. CRC CRITICAL REVIEWS IN BIOCHEMISTRY, 1985, 17 (04): : 313 - 451
  • [87] ENZYME STEREOSPECIFICITIES FOR NICOTINAMIDE NUCLEOTIDES
    YOU, KS
    ARNOLD, LJ
    ALLISON, WS
    KAPLAN, NO
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1978, 3 (12) : 265 - 268
  • [88] NUCLEAR MAGNETIC-RESONANCE STUDIES ON PYRIDINE DINUCLEOTIDES .2. SOLUTION CONFORMATIONAL DYNAMICS OF NICOTINAMIDE ADENINE-DINUCLEOTIDE AND NICOTINAMIDE MONONUCLEOTIDE AS VIEWED BY PROTON T1 MEASUREMENTS
    ZENS, AP
    WILLIAMS, TJ
    WISOWATY, JC
    FISHER, RR
    DUNLAP, RB
    BRYSON, TA
    ELLIS, PD
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1975, 97 (10) : 2850 - 2857