Engineering sulfotransferases to modify heparan sulfate

被引:63
作者
Xu, Ding [1 ]
Moon, Andrea F. [2 ]
Song, Danyin [1 ]
Pedersen, Lars C. [2 ]
Liu, Jian [1 ]
机构
[1] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA
[2] Natl Inst Environm Hlth Sci, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nchembio.66
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The biosynthesis of heparan sulfate (HS) involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations of these residues altered the substrate specificities. Our results demonstrate the feasibility of tailoring the specificity of sulfotransferases to modify HS with desired functions.
引用
收藏
页码:200 / 202
页数:3
相关论文
共 12 条
[1]   Using an enzymatic combinatorial approach to identify anticoagulant heparan sulfate structures [J].
Chen, Jinghua ;
Jones, Courtney L. ;
Liu, Jian .
CHEMISTRY & BIOLOGY, 2007, 14 (09) :986-993
[2]  
DeLano W. L., 2002, PYMOL
[3]   Sulfation patterns of glycosaminoglycans encode molecular recognition and activity [J].
Gama, Cristal I. ;
Tully, Sarah E. ;
Sotogaku, Naoki ;
Clark, Peter M. ;
Rawat, Manish ;
Vaidehi, Nagarajan ;
Goddard, William A., III ;
Nishi, Akinori ;
Hsieh-Wilson, Linda C. .
NATURE CHEMICAL BIOLOGY, 2006, 2 (09) :467-473
[4]   Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1 [J].
Kakuta, Y ;
Sueyoshi, T ;
Negishi, M ;
Pedersen, LC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) :10673-10676
[5]   Crystal structure of estrogen sulphotransferase [J].
Kakuta, Y ;
Pedersen, LG ;
Carter, CW ;
Negishi, M ;
Pedersen, LC .
NATURE STRUCTURAL BIOLOGY, 1997, 4 (11) :904-908
[6]   MOLSCRIPT - A PROGRAM TO PRODUCE BOTH DETAILED AND SCHEMATIC PLOTS OF PROTEIN STRUCTURES [J].
KRAULIS, PJ .
JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1991, 24 :946-950
[7]   Enzymatic synthesis of antithrombin III-binding heparan sulfate pentasaccharide [J].
Kuberan, B ;
Lech, MZ ;
Beeler, DL ;
Wu, ZLL ;
Rosenberg, RD .
NATURE BIOTECHNOLOGY, 2003, 21 (11) :1343-1346
[8]   Anticoagulant heparan sulfate: structural specificity and biosynthesis [J].
Liu, Jian ;
Pedersen, Lars C. .
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 2007, 74 (02) :263-272
[9]   Raster3D: Photorealistic molecular graphics [J].
Merritt, EA ;
Bacon, DJ .
MACROMOLECULAR CRYSTALLOGRAPHY, PT B, 1997, 277 :505-524
[10]   C-13-NMR relaxation study of heparin-disaccharide interactions with tripeptides GRG and GKG [J].
Mikhailov, D ;
Mayo, KH ;
Pervin, A ;
Linhardt, RJ .
BIOCHEMICAL JOURNAL, 1996, 315 :447-454