二氢蝶啶还原酶的结构和机制特征：含Tyr-(Xaa)3-Lys还原酶和脱氢酶家族的成员

Varughese K I, Xuong N H, Kiefer P M, Matthews D A, Whiteley J M

University of California at San Diego, La Jolla 92093-0317.

Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5582-6. doi: 10.1073/pnas.91.12.5582.

Dihydropteridine reductase (EC 1.6.99.7) is a member of the recently identified family of proteins known as short-chain dehydrogenases. When the x-ray structure of dihydropteridine reductase is correlated with conserved amino acid sequences characteristic of this enzyme class, two important common structural regions can be identified. One is close to the protein N terminus and serves as the cofactor binding site, while a second conserved feature makes up the inner surface of an alpha-helix in which a tyrosine side chain is positioned in close proximity to a lysine residue four residues downstream in the sequence. The main function of this Tyr-Lys couple may be to facilitate tyrosine hydroxyl group participation in proton transfer. Thus, it appears that there is a distinctive common mechanism for this group of short-chain or pyridine dinucleotide-dependent oxidoreductases that is different from their higher molecular weight counterparts.

二氢蝶啶还原酶（EC 1.6.99.7）是最近鉴定出的被称为短链脱氢酶的蛋白质家族成员。当二氢蝶啶还原酶的X射线结构与该酶类的保守氨基酸序列相关联时，可以识别出两个重要的共同结构区域。一个靠近蛋白质N端，作为辅因子结合位点，而第二个保守特征构成α螺旋的内表面，其中酪氨酸侧链位于序列中四个残基下游的赖氨酸残基附近。这个酪氨酸-赖氨酸对的主要功能可能是促进酪氨酸羟基参与质子转移。因此，似乎这组短链或吡啶二核苷酸依赖性氧化还原酶有一种独特的共同机制，与它们分子量较大的对应物不同。