ALDEHYDE DEHYDROGENASES - WIDESPREAD STRUCTURAL AND FUNCTIONAL DIVERSITY WITHIN A SHARED FRAMEWORK

被引:166
作者
HEMPEL, J
NICHOLAS, H
LINDAHL, R
机构
[1] CARNEGIE MELLON UNIV,PITTSBURGH SUPERCOMP CTR,PITTSBURGH,PA 15213
[2] UNIV S DAKOTA,SCH MED,DEPT BIOCHEM & MOLEC BIOL,VERMILLION,SD 57069
关键词
ACTIVE SITE; ALDEHYDE DEHYDROGENASE; CONSERVED FOLDING; GLYCINE CONSERVATION; NAD-BINDING DOMAIN; PROTEIN EVOLUTION; PROTEIN FAMILY;
D O I
10.1002/pro.5560021111
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
Sequences of 16 NAD and/or NADP-linked aldehyde oxidoreductases are aligned, including representative examples of all aldehyde dehydrogenase forms with wide substrate preferences as well as additional types with distinct specificities for certain metabolic aldehyde intermediates, particularly semialdehydes, yielding pairwise identities from 15 to 83%. Eleven of 23 invariant residues are glycine and three are proline, indicating evolutionary restraint against alteration of peptide chain-bending points. Additionally, another 66 positions show high conservation of residue type, mostly hydrophobic residues. Ten of these occur in predicted beta-strands, suggesting important interior-packing interactions. A single invariant cysteine residue is found, further supporting its catalytic role. A previously identified essential glutamic acid residue is conserved in all but methyl malonyl semialdehyde dehydrogenase, which may relate to formation by that enzyme of a CoA ester as a product rather than a free carboxylate species. Earlier, similarity to a GXGXXG segment expected in the NAD-binding site was noted from alignments with fewer sequences. The same region continues to be indicated, although now only the first glycine residue is strictly conserved and the second (usually threonine) is not present at all, suggesting greater variance in coenzyme-binding interactions.
引用
收藏
页码:1890 / 1900
页数:11
相关论文
共 63 条
  • [1] ABOLA EE, 1987, CRYSTALLOGRAPHIC DAT, P107
  • [2] ACTIVE-SITE OF HUMAN-LIVER ALDEHYDE DEHYDROGENASE
    ABRIOLA, DP
    FIELDS, R
    STEIN, S
    MACKERELL, AD
    PIETRUSZKO, R
    [J]. BIOCHEMISTRY, 1987, 26 (18) : 5679 - 5684
  • [3] [Anonymous], 1993, PROTEINS STRUCTURES
  • [4] [Anonymous], 1999, INTRO PROTEIN STRUCT
  • [5] [Anonymous], PREDICTION PROTEIN S
  • [6] ARGOS P, 1989, PROTEIN STRUCTURE PR, V3, P169
  • [7] PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
    BERNSTEIN, FC
    KOETZLE, TF
    WILLIAMS, GJB
    MEYER, EF
    BRICE, MD
    RODGERS, JR
    KENNARD, O
    SHIMANOUCHI, T
    TASUMI, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1977, 112 (03) : 535 - 542
  • [8] EYE LENS ZETA-CRYSTALLIN RELATIONSHIPS TO THE FAMILY OF LONG-CHAIN ALCOHOL POLYOL DEHYDROGENASES - PROTEIN TRIMMING AND CONSERVATION OF STABLE PARTS
    BORRAS, T
    PERSSON, B
    JORNVALL, H
    [J]. BIOCHEMISTRY, 1989, 28 (15) : 6133 - 6139
  • [9] EMPIRICAL PREDICTIONS OF PROTEIN CONFORMATION
    CHOU, PY
    FASMAN, GD
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1978, 47 : 251 - 276
  • [10] CLARK SP, 1992, COMPUT APPL BIOSCI, V8, P535