Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1
Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1
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DOI：
10.1074/jbc.274.16.10673
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发表时间：
1999-04-16
影响因子：
4.8
通讯作者：
Pedersen, LC
中科院分区：
文献类型：
--
作者：
Kakuta, Y;Sueyoshi, T;Pedersen, LC
硫酸乙酰肝素N-脱乙酰基酶/N-磺基转移酶（HSNST）催化硫酸乙酰肝素和肝素生物合成中的第一步和强制性步骤。人HSNST-1的磺基转移酶结构域（NST 1）的晶体结构已在2.3埃分辨率下在与5 ′-磷酸3 ′-磷酸腺苷（PAP）的二元复合物中确定，NST 1近似球形，具有开放裂缝，并且由单个α/β折叠组成，其具有中心五链平行β折叠和带有链间二硫键的三链反平行β折叠。结构区域α 1，α 6，β 1，β 7，5 '-磷酸硫酸盐结合环（介于β 1和α 1之间）和无规卷曲NST 1的α 6和α 13（β 8和α 13之间）构成了NST 1的PAP结合位点，在PAP分子的5 '-磷酸盐附近形成开放裂缝（在β 2和α 2之间），可以为底物结合提供相互作用。保守残基Lys-614位于与5 '-磷酸的桥氧形成氢键的位置。
Heparan sulfate N-deacetylase/N-sulfotransferase (HSNST) catalyzes the first and obligatory step in the biosynthesis of heparan sulfates and heparin, The crystal structure of the sulfotransferase domain (NST1) of human HSNST-1 has been determined at 2.3-Angstrom resolution in a binary complex with 3'-phosphoadenosine 5'-phosphate (PAP), NST1 is approximately spherical with an open cleft, and consists of a single alpha/beta fold with a central five-stranded parallel beta-sheet and a three-stranded anti-parallel beta-sheet bearing an interstrand disulfide bond. The structural regions alpha 1, alpha 6, beta 1, beta 7, 5'-phosphosulfate binding loop (between beta 1 and alpha 1), and a random coil (between beta 8 and alpha 13) constitute the PAP binding site of NST1, The alpha 6 and random coil (between beta 2 and alpha 2), which form an open cleft near the 5'-phosphate of the PAP molecule, may provide interactions for substrate binding. The conserved residue Lys-614 is in position to form a hydrogen bond with the bridge oxygen of the 5'-phosphate.