Rational proteomics I. Fingerprint identification and cofactor specificity in the short-chain oxidoreductase (SCOR) enzyme family
Rational proteomics I. Fingerprint identification and cofactor specificity in the short-chain oxidoreductase (SCOR) enzyme family
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DOI：
10.1002/prot.10512
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发表时间：
2003-12-01
影响因子：
2.9
通讯作者：
Weeks, CM
中科院分区：
文献类型：
--
作者：
Duax, WL;Pletnev, V;Weeks, CM
短链氧化还原酶(SCOR)家族包括2000多个成员，在测序的基因组中被鉴定。在这些酶中，类似于200种的酶已被功能鉴定，类似于40的三维晶体结构已被报道。由于一些SCOR酶与高血压、糖尿病、乳腺癌和多囊肾病有关，因此确定目前尚不清楚其生物学功能的家族其他成员的特征是很重要的。虽然，SCOR家族似乎只有一个完全保守的残基，但使用生物信息学方法，有可能确定由30-40个残基组成的特征指纹，这些残基在SCOR亚组中保守在70%或更高水平。这些指纹可以可靠地预测几个重要的结构功能特征，包括NAD/NADP辅助因子偏好。例如，天冬氨酸或精氨酸残基分别与NAD或NADP结合的相关性，预测了70%以上功能未知的SCOR蛋白的辅因子偏好。对辅因子周围保守残基的分析表明，大多数SCOR晶体结构中存在以前未检测到的CH...O氢键，预测90%的未知功能的SCOR蛋白中存在类似的氢键，并表明这些氢键可能在这些酶的催化功能中发挥关键作用。(C)2003年Wiley-Liss，Inc.
The short-chain oxidoreductase (SCOR) family of enzymes includes over 2000 members identified in sequenced genomes. Of these enzymes, similar to200 have been characterized functionally, and the three-dimensional crystal structures of similar to40 have been reported. Since some SCOR enzymes are involved in hypertension, diabetes, breast cancer, and polycystic kidney disease, it is important to characterize the other members of the family for which the biological functions are currently unknown. Although, the SCOR family appears to have only a single fully conserved residue, it was possible, using bioinformatics methods, to determine characteristic fingerprints composed of 30-40 residues that are conserved at the 70% or greater level in SCOR subgroups. These fingerprints permit reliable prediction of several important structure-function features including NAD/NADP cofactor preference. For example, the correlation of aspartate or arginine residues with NAD or NADP binding, respectively, predicts the cofactor preference of more than 70% of the SCOR proteins with unknown function. The analysis of conserved residues surrounding the cofactor has revealed the presence of previously undetected CH...O hydrogen bonds in the majority of the SCOR crystal structures, predicts the presence of similar hydrogen bonds in 90% of the SCOR proteins of unknown function, and suggests that these hydrogen bonds may play a critical role in the catalytic functions of these enzymes. (C) 2003 Wiley-Liss, Inc.