叶升

浙江大学生命科学研究院教授、研究员、博士生导师。

办公地点：医学院科研楼A210
电话：0571-88981521
传真：0571-88981521
Email：sye@zju.edu.cn

实验室网站：http://lsi.zju.edu.cn/yjdw_detail.aspx?ID=13

• 1987-1991 厦门大学细胞生物学学士
• 1991-1996 中国科学院生物物理研究所生物物理学博士
• 1996-1999 美国贝勒医学院生物化学系博士后
• 1999-2001 美国得克萨斯大学西南医学中心生物化学系博士后

• 2001-2003 美国Syrrx公司科学家
• 2003-2005 美国德州农工医学中心科学家
• 2005-2010 美国得克萨斯大学西南医学中心生理学系/霍华德-休斯医学研究所，讲师—二级研究专家—助理教授
• 2010至今 浙江大学生命科学研究院教授

生命的分子机器。如果把复杂的生命活动过程分解为一个个单独的物理、化学过程，这些过程依赖于细胞内各式各样结构复杂而有序的分子机器来进行，这些分子机器由蛋白质、核酸、糖类、脂类等生物大分子或这些大分子的复合物构成。正是依靠了生命体内微观世界中众多的分子机器的有序运转、协同配合，生命体才有了活力。

构成生物大分子的原子主要是氢、碳、氮、氧、磷、硫以及少量的金属原子，这些普通的原子一旦在三维空间中特定地排列，就使得这个生物大分子成为一个分子机器，能执行特定的生命功能。形象地说，本课题组的研究方向就是要把细胞中重要的分子机器打开来看一看，了解什么样的结构导致这些分子机器具有特定的功能，这些功能又是如何精确地被其它外界因素调控的。通过研究结构与功能的关系来回答一些重要的生物学问题。这些重要生物学问题的回答一方面是充分认识生命现象本质，掌握生命活动规律所必须的，具有重大的科学和认识价值。另一方面，这些研究成果可以应用于社会生产，对人类的经济生活产生重大影响。

1. Ye S, Li Y, Jiang Y. Novel insights into ion selectivity from high resolution structures of an open K+ channel pore. Nat Struct Mol Biol. 2010 Epub 2010 August 1. (通讯作者)
2. Wu Y, Yang Y, Ye S, Jiang Y. Structure of the Gating Ring from the Human High-conductance Ca2+-gated K+ Channel. Nature. 2010 466:393-7. Epub 2010 Jun 23.
3. Ye S, Li Y, Chen L, Jiang Y. Crystal structures of a Ligand-free MthK gating ring: Insights into the ligand gating mechanism of K+ channel. Cell. 2006 126:1161-73.
4. Ye S, Vakonakis I, Ioerger TR, LiWang AC, Sacchettini JC. Crystal structure of circadian clock protein KaiA from Synechococcus elongatus. J Biol Chem. 2004 279:20511-20518. Epub 2004 Mar 8. 【PDF】
5. Aertgeerts K, Ye S, Tennant MG, et al. Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation. Protein Sci. 2004 13:412-421. Epub 2004 Jan 10.
6. Ye S, Goldsmith EJ. Serpins and Other Covalent Protease Inhibitors. Curr Opin Struct Biol. 2001 11:740-745. (特邀综述)
7. Ye S, Cech AL, Belmares R, et al. The structure of a Michaelis Serpin-Protease Complex. Nat Struct Biol. 2001 8:979-983.
8. Ye S, Luo Y, Lu W, et al. Structural Basis for Interaction of FGF-1, FGF-2 and FGF-7 with Different Heparan Sulfate Motifs. Biochemistry. 2001 40:14429-14439.
9. Ye S, Wan ZL, Liu CG, Chang WR, Liang DC. Crystal structure of (L-Arg)-B0 bovine insulin at 0.21 nm resolution. Science in China (Series C). 1996 26:295-301 (Chinese Ed.); 39:465-473 (Eng. Ed.).

在Syrrx公司（Syrrx公司于2005年2月7日为日本武田制药公司收购成为武田-圣地亚哥分部）担任科学家期间，作为基于结构的糖尿病药物设计主要参与人之一，所设计的高选择性双肽蛋白酶4抑制剂已通过临床试验。武田制药于2008年1月7日向美国食品与药物管理局（FDA）递交2型糖尿病新药申请（药名alogliptin），2010年6月27日FDA以所提供数据不足为理由拒绝批准此新药申请，武田制药决定增补数据预期在两年之内再次递交此新药申请；此外，武田制药于2008年9月23日向FDA递交2型糖尿病复方药新药申请（药名alogliptin/Actos）。

1. Luo Y, Ye S, Kan M, McKeehan WL. Control of FGF7- and FGF1-induced mitogenesis and downstream signaling by distinct heparin octasaccharide motifs. J Biol Chem. 2006 281:21052-61. Epub 2006 May 25.
2. Shi N, Ye S, Alam A, Chen L, Jiang Y. Atomic Structure of a Na+ and K+ Conducting Channel. Nature. 2006 440:570-574. Epub 2006 Feb 8. 【PDF】
3. Luo Y, Ye S, Kan M, McKeehan WL. Structural Specificity in a FGF7-Affinity Purified Heparin Octasaccharide Required for Formation of a Complex with FGF7 and FGFR2IIIb. J Cell Biochem. 2006 97:1241-1258. Epub 2005 Nov 28.
4. Paricharttanakul NM, Ye S, Menefee AL, et al. Kinetic and structural Characterization Phosphofructokinase from Lactobacillus bulgaricus. Biochemistry. 2005 44:15280-15286.
5. Ye S, Vakonakis I, Ioerger TR, LiWang AC, Sacchettini JC. Crystal structure of circadian clock protein KaiA from Synechococcus elongatus. J Biol Chem. 2004 279:20511-20518. Epub 2004 Mar 8.
6. Aertgeerts K, Ye S, Shi L, et al. N-linked glycosylation of dipeptidyl peptidase IV (CD26): Effects on enzyme activity, homodimer formation, and adenosine deaminase binding. Protein Sci. 2004 13:145-154.
7. Ye S, von Delft F, Brooun A, Knuth MW, Swanson RV, McRee DE. The Crystal Structure of Shikimate Dehydrogenase (AroE) Reveals a Unique NADPH Binding Mode. J Bacteriol. 2003 185:4144-4151. 【PDF】
8. Bergstrom RC, Coombs GS, Ye S, Madison EL, Goldsmith EJ, Corey DR. Binding of nonphysiological protein and peptide substrates to proteases: differences between urokinase-type plasminogen activator and trypsin and contributions to the evolution of regulated proteolysis. Biochemistry. 2003 42:5395-5402.
9. Ye S, Wan ZL, Zhou B, Jing GZ, Liang DC. Crystallization and preliminary X-ray analysis of SNR 141 - an N-terminal fragment of staphylococcal nuclease R. Chinese Science Bulletin. 1997 42:983-985 (Chinese Ed.); 42:957-960 (Eng. Ed.).
10. Ye S, Wan ZL, Shi YZ, Zhou B, Jing GZ, Liang DC. Crystallization and preliminary X-ray analysis of staphylococcal nuclease R. Acta Biophysica Sinica. 1997 13:7-10.

1. Brooun A, Hosfield DJ, Skene RJ, Tari LW, Ye S. Crystal structure of MVAS. Date of Patent: July 11, 2006, Assignee: Takeda San Diego, Inc., San Diego, CA (US), Patent No. US 7,076,372.
2. Brooun A, Hosfield DJ, Skene RJ, Tari LW, Ye S. Crystallization of MVAS. Date of Patent: August 7, 2007, Assignee: Takeda San Diego, Inc., San Diego, CA (US), Patent No. US 7,252,930.
3. Aertgeerts K, Prasad S, Sridhar V, Wijnands RA, Ye S. Crystallization of Fibroblast Activation Protein Alpha (FAP). Date of Patent: November 20, 2007, Assignee: Takeda San Diego, Inc., San Diego, CA (US), Patent No. US 7,297,508.
4. Aertgeerts K, Cronin CN, Hosfield DJ, Knuth MW, McRee DE, Prasad S, Sang B, Skene RJ, Wijnands RA, Ye S. Crystallization of Dipeptidyl Peptidase IV (DPPIV). Date of Patent: March 18, 2008, Assignee: Takeda San Diego, Inc., San Diego, CA (US), Patent No. US 7,344,852.

• Ye S, Li Y, Jiang Y. Novel insights into ion selectivity from high resolution structures of an open K+ channel pore. Nat Struct Mol Biol. 2010;17(8):1019-1023.
• Wu Y, Yang Y, Ye S, Jiang Y. Structure of the gating ring from the human high-conductance Ca2+-gated K+ channel. Nature. 2010;466(7304):393-397.
• Ye S, Li Y, Chen L, Jiang Y. Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels. Cell. 2006;126(6):1161-1173.
• Ye S, Vakonakis I, Ioerger TR, LiWang AC, Sacchettini JC. Crystal structure of circadian clock protein KaiA from Synechococcus elongatus. J Biol Chem. 2004;279(19):20511-20518.
• Aertgeerts K, Ye S, Tennant MG, et al. Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation. Protein Sci. 2004;13(2):412-421.
• Ye S, Goldsmith EJ. Serpins and other covalent protease inhibitors. Curr Opin Struct Biol. 2001;11(6):740-745.
• Ye S, Cech AL, Belmares R, et al. The structure of a Michaelis serpin-protease complex. Nat Struct Biol. 2001;8(11):979-983.
• Ye S, Luo Y, Lu W, et al. Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs. Biochemistry. 2001;40(48):14429-14439.
• Shi N, Ye S, Alam A, Chen L, Jiang Y. Atomic structure of a Na+- and K+-conducting channel. Nature. 2006;440(7083):570-574.
• Ye S, von Delft F, Brooun A, Knuth MW, Swanson RV, McRee DE. The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode. J Bacteriol. 2003;185(14):4144-4151.
• Doyle DA, Morais Cabral J, Pfuetzner RA, et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998;280(5360):69-77.
• Jiang Y, Lee A, Chen J, et al. X-ray structure of a voltage-dependent K+ channel. Nature. 2003;423(6935):33-41.
• Ishida N, Katsu T, Oishi K, et al. Crystal structure of the circadian clock protein KaiC. Mol Cell. 2001;8(5):1093-1104.
• Hirayama J, Sassone-Corsi P. Structural and functional features of the circadian clock. Cold Spring Harb Symp Quant Biol. 2007;72:115-124.
• Jiang Y, Lee A, Chen J, et al. Crystal structure and mechanism of a calcium-gated potassium channel. Nature. 2002;417(6888):515-522.