Schuchman E H, Jackson C E, Desnick R J
Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029.
Genomics. 1990 Jan;6(1):149-58. doi: 10.1016/0888-7543(90)90460-c.
cDNAs encoding the human lysosomal hydrolase, arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase, EC 3.1.6.1), were isolated from a hepatoma cell cDNA library using an ASB-specific oligonucleotide generated by the MOPAC (mixed oligonucleotide primed amplification of cDNA) technique. To facilitate cDNA cloning, human ASB was purified to apparent homogeneity and a total of 112 amino acid residues were microsequenced from the N-terminus and four internal tryptic peptides of the 47-kDa subunit. Based on the ASB N-terminal amino acid sequence, two oligonucleotide mixtures containing inosines to reduce the mixture complexity were constructed and used as primers to amplify an ASB-specific product from human placental cDNA by the polymerase chain reaction. DNA sequencing of this MOPAC product demonstrated colinearity with 21 N-terminal ASB amino acids. Based on this sequence and on codon usage for the adjacent conserved amino acids in human arylsulfatases A and C, a unique 66-mer was synthesized and used to screen a human hepatoma cell cDNA library. Four putative positive cDNA clones were isolated, and the largest insert (pASB-1) was sequenced in both orientations. The 1834-bp pASB-1 insert had a 1278-bp open reading frame encoding 425 amino acids that was colinear with 85 microsequenced amino acids of the purified enzyme, demonstrating its authenticity. Using the pASB-1 cDNA as a probe, a full-length cDNA clone, pASB-4, was isolated from a human testes library and sequenced in both orientations. pASB-4 had a 2811-bp insert containing a 559-bp 5' untranslated sequence, a 1602-bp open reading frame encoding 533 amino acids (six potential N-glycosylation sites), a 641-bp 3' untranslated sequence, and a 9-bp poly(A) tract. Comparison of the predicted amino acid sequences of arylsulfatases A, B, and C revealed regions of identity, particularly in their N-termini.
利用MOPAC(混合寡核苷酸引发的cDNA扩增)技术产生的芳基硫酸酯酶B(ASB;N-乙酰半乳糖胺-4-硫酸酯酶,EC 3.1.6.1)特异性寡核苷酸,从肝癌细胞cDNA文库中分离出编码人溶酶体水解酶的cDNA。为便于cDNA克隆,将人ASB纯化至表观均一,并从47 kDa亚基的N端和四个内部胰蛋白酶肽段对总共112个氨基酸残基进行了微量测序。根据ASB的N端氨基酸序列,构建了两种含有次黄苷以降低混合物复杂性的寡核苷酸混合物,并用作引物,通过聚合酶链反应从人胎盘cDNA中扩增出ASB特异性产物。该MOPAC产物的DNA测序表明其与21个ASB N端氨基酸具有共线性。基于该序列以及人芳基硫酸酯酶A和C中相邻保守氨基酸的密码子使用情况,合成了一个独特的66聚体,并用于筛选人肝癌细胞cDNA文库。分离出四个推定的阳性cDNA克隆,并对最大的插入片段(pASB-1)进行了双向测序。1834 bp的pASB-1插入片段有一个1278 bp的开放阅读框,编码425个氨基酸,与纯化酶的85个微量测序氨基酸具有共线性,证明了其真实性。以pASB-1 cDNA为探针,从人睾丸文库中分离出一个全长cDNA克隆pASB-4,并进行了双向测序。pASB-4有一个2811 bp的插入片段,包含一个559 bp的5'非翻译序列、一个1602 bp的开放阅读框,编码533个氨基酸(六个潜在的N-糖基化位点)、一个641 bp的3'非翻译序列和一个9 bp的聚腺苷酸尾。芳基硫酸酯酶A、B和C的预测氨基酸序列比较揭示了相同区域,特别是在它们的N端。