Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non-active-site substitutions.
Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non-active-site substitutions.
复制标题
人β1β1醇脱氢酶的结构：非活性位点取代的催化作用。
DOI：
10.1073/pnas.88.18.8149
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发表时间：
1991
影响因子：
11.1
通讯作者：
Amzel,LM
中科院分区：
文献类型：
--
作者：
Hurley,TD;Bosron,WF;Hamilton,JA;Amzel,LM
通过X射线晶体学测定了与NAD+复合的人β 1 β 1醇脱氢酶（ADH; EC 1.1.1.1）的三维结构，分辨率为3.0-A。在马EE和人β 1 β 1醇脱氢酶之间，除了一种情况外，所有直接参与辅酶结合的氨基酸都是保守的[位置48处的丝氨酸（马）与苏氨酸（人）]。结果，辅酶分子以类似的方式结合在两种酶中。然而，在NAD+的焦磷酸桥附近的相互作用的强度似乎在人类酶中增强。Arg-47和Asp-50的侧链移动和包含残基202-212的螺旋位置的移位可以解释在人酶与马酶中观察到的Vmax降低和NADH解离速率降低。这些催化差异似乎不是由于直接参与辅酶结合的任何氨基酸的取代，而是由于两种酶之间的多个序列差异导致的结构重排的结果。
The three-dimensional structure of human beta 1 beta 1 alcohol dehydrogenase (ADH; EC 1.1.1.1) complexed with NAD+ has been determined by x-ray crystallography to 3.0-A resolution. The amino acids directly involved in coenzyme binding are conserved between horse EE and human beta 1 beta 1 alcohol dehydrogenase in all but one case [serine (horse) vs. threonine (human) at position 48]. As a result, the coenzyme molecule is bound in a similar manner in the two enzymes. However, the strength of the interactions in the vicinity of the pyrophosphate bridge of NAD+ appears to be enhanced in the human enzyme. Side-chain movements of Arg-47 and Asp-50 and a shift in the position of the helix comprising residues 202-212 may explain both the decreased Vmax and the decreased rate of NADH dissociation observed in the human enzyme vs. the horse enzyme. It appears that these catalytic differences are not due to substitutions of any amino acids directly involved in coenzyme binding but are the result of structural rearrangements resulting from multiple sequence differences between the two enzymes.
DOI：
--
发表时间：
1980
期刊：
影响因子：
--
作者：
P. Argos;M. Rossman
通讯作者：
M. Rossman