Sardana V V, Wolfgang J A, Veloski C A, Long W J, LeGrow K, Wolanski B, Emini E A, LaFemina R L
Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486-0004.
J Biol Chem. 1994 May 20;269(20):14337-40.
The human cytomegalovirus UL80 gene encodes an 80-kDa precursor polyprotein whose N-terminal 256-amino acid domain is a protease. This enzyme cleaves a specific peptide bond that results in its own release from the precursor, as well as a peptide bond near the C terminus of the viral assembly protein. The latter cleavage is apparently required for encapsidation of the viral genomic DNA and maturation of the viral capsid. A series of peptide substrates, representing the assembly protein cleavage site, was used to study the enzyme's substrate requirements and specificity. It was found that efficient cleavage minimally required the amino acid residues spanning the P4 to P4' positions. Substitution at any of these residues adversely affected the reaction. Conservation of the hydrophobic residues at P3 and P4 was essential. In addition, cleavage of a peptide representing the protease domain release site was reduced almost 100-fold relative to cleavage of the assembly protein maturation site peptide substrate.
人巨细胞病毒UL80基因编码一种80 kDa的前体多蛋白，其N端256个氨基酸结构域是一种蛋白酶。该酶切割一个特定的肽键，导致其自身从前体中释放出来，以及在病毒装配蛋白C端附近切割一个肽键。后一种切割显然是病毒基因组DNA包装和病毒衣壳成熟所必需的。一系列代表装配蛋白切割位点的肽底物被用于研究该酶的底物需求和特异性。发现有效切割至少需要跨越P4到P4'位置的氨基酸残基。这些残基中任何一个的取代都会对反应产生不利影响。P3和P4处疏水残基的保守是必不可少的。此外，相对于装配蛋白成熟位点肽底物的切割，代表蛋白酶结构域释放位点的肽的切割减少了近100倍。
