Evolution of catalytic and regulatory sites in phosphorylases
Evolution of catalytic and regulatory sites in phosphorylases
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DOI：
10.1038/313500a0
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发表时间：
1985-02
期刊：
影响因子：
64.8
通讯作者：
D. Palm;R. Goerl;K. Burger
中科院分区：
文献类型：
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作者：
D. Palm;R. Goerl;K. Burger
糖原磷酸化酶（E.C.2.4.1.1）是第一个被证明受变构效应子1和蛋白质磷酸化2调节的酶。细菌磷酸化酶3的转录控制进一步扩展了磷酸化酶有助于控制碳水化合物代谢的调节机制的范围。尽管它们的调节差异，所有已知的磷酸化酶都具有催化和结构特性4，5和高度保守的吡哆醛-5 ′-磷酸结合位点6 -9;这使得磷酸化酶对于研究调节机制的进化具有高度吸引力10。测定了兔肌磷酸化酶的一级结构6和三级结构4，11- 17。最近，来自植物18、19和细菌20的可比氨基酸序列已经解析。本文报道了大肠杆菌麦芽糖糊精磷酸化酶的687个氨基酸的序列。动物和细菌磷酸化酶序列的比对显示出在封闭外部催化区的多肽链的91%中具有很强的同源性（48%）。在该区域内，结构同源性鉴定了一个假定的磷酸结合位点，从该位点可能发展出兔肌肉磷酸化酶的变构5′ AMP结合位点。从减少对齐在N-末端和存在额外的残基相比，细菌磷酸化酶，我们得出结论，调节序列，也携带磷酸化位点的肌肉酶加入到一个假定的祖先前体基因的基因融合分离后的真核和原核细胞系的血统。
Glycogen phosphorylase (E.C.2.4.1.1) was the first enzyme shown to be regulated by allosteric effectors1and by protein phosphorylation2. Transcriptional control of bacterial phosphorylases3further extends the range of regulatory mechanisms by which phosphorylases contribute to the control of carbohydrate metabolism. Despite their regulatory differences, all known phosphorylases share catalytic and structural properties4,5and a strongly conserved pyridoxal-5′-phosphate binding site6–9; this makes phosphorylases highly attractive for investigations into the evolution of regulatory mechanisms10. The primary6and tertiary4,11–17structure of rabbit muscle phosphorylase has been determined completely. Recently, comparable amino acid sequences from plants18,19and bacteria20have been resolved. Here we report the sequence of 687 amino acids ofEscherichia colimaltodextrin phosphorylase, deduced from a clonedmalPgene sequence. Alignment of animal and bacterial phosphorylase sequences shows strong homology (48%) throughout 91% of the polypeptide chain enclosing the extrinsic catalytic region. Within this region, structural homology identifies a presumed phosphate-binding site from which the allosteric 5′ AMP binding site of rabbit muscle phosphorylase might have developed. From the decreased alignment at the N-terminus and the presence of additional residues compared with bacterial phosphorylases, we conclude that the regulatory sequences that also carry the phosphorylation site in the muscle enzyme were joined to a presumed ancestral precursor gene by gene fusion after separation of the eukaryotic and prokaryotic lines of descent.