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首页> 外文期刊>Life sciences >Importance of the substrate-binding loop region of human monomeric carbonyl reductases in catalysis and coenzyme binding.
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Importance of the substrate-binding loop region of human monomeric carbonyl reductases in catalysis and coenzyme binding.

机译：人类单体羰基还原酶的底物结合环区域在催化和辅酶结合中的重要性。

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AIMS: Monomeric carbonyl reductase 1 (CBR1) and 3 (CBR3) are members of the short-chain dehydrogenase/reductase superfamily, and metabolize endogenous and xenobiotic compounds using NADPH as a coenzyme. CBR3 exhibits a higher K(m) value toward NADPH and more limited carbonyl reductase activities than CBR1, although they are highly homologous to each other in amino acid sequence levels. In the present study, we investigated the origin of the different properties of the enzymes by analyses using several chimeric enzymes. MAIN METHODS: Harr-plot analysis of the amino acid sequences was conducted and as a result, two low-identity regions between human CBR1 and CBR3 were found: these were designated as the N-terminal low-identity region (LirN) and the C-terminal low-identity region (LirC; the substrate-binding region). We genetically constructed chimeric enzymes while focusing on these regions. KEY FINDINGS: Chimeric CBR1 possessing LirN of CBR3 (CBR1LirN3) exhibited CBR1-like activities but a low coenzyme affinity probably due to a structural alteration in a micro domain, whereas chimeric CBR1 including LirC of CBR3 (CBR1LirC3) was enzymatically similar to CBR3. Furthermore, CBR3LirC1 was similar to CBR1 in both enzymatic activities and coenzyme binding. SIGNIFICANCE: These results suggested that LirC, i.e., the substrate-binding loop region, is the origin of the difference between human CBR1 and CBR3 in both catalytic and coenzyme-binding properties.
机译：目的：单体羰基还原酶1（CBR1）和3（CBR3）是短链脱氢酶/还原酶超家族的成员，并使用NADPH作为辅酶代谢内源性和异源性化合物。尽管CBR3在氨基酸序列水平上彼此高度同源，但它们对NADPH的K（m）值更高，并且羰基还原酶的活性更有限。在本研究中，我们通过使用几种嵌合酶的分析研究了酶不同性质的起源。主要方法：对氨基酸序列进行了Harr-plot分析，结果发现了人CBR1和CBR3之间的两个低同一性区域：分别被指定为N末端低同一性区域（LirN）和C -末端低同一性区域（LirC;底物结合区域）。我们着眼于这些区域的同时，通过基因构建嵌合酶。关键发现：具有CBR3的LirN的嵌合CBR1（CBR1LirN3）表现出CBR1样的活性，但辅酶亲和力低，这可能是由于微结构域的结构改变所致，而包括CBR3的LirC的嵌合CBR1（CBR1LirC3）在酶学上与CBR3相似。此外，CBR3LirC1在酶活性和辅酶结合方面均类似于CBR1。意义：这些结果表明，LirC，即底物结合环区域，是人类CBR1和CBR3在催化和辅酶结合特性上差异的起源。

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