title: Homology modeling and docking studies of ENPP4: a BCG activated tumoricidal macrophage protein.
abstract: BACKGROUND
  The 3D structure and functions of ENPP4, a protein expressed on the surface of Bacillus Calmette-Guerin (BCG)-activated macrophages, are unknown. In this study, we analyzed the 3D structure of ENPP4 and determined its tumoricidal effects on MCA207 cells.
  
  
  RESULTS
  Homology modeling showed that Arg305, Tyr341, Asn291, and Asn295 are important residues in substrate, adenosine triphosphate (ATP), binding. A molecular dynamics study was also carried out to study the stability of ENPP4 (including zinc atoms) as well as its ligand-enzyme complex. BCG increased ENPP4 expression in macrophages, and specific blocking of ENPP4 in BCG-activated macrophages (BAMs) significantly reduced their cytotoxicity against MCA207 cells.
  
  
  CONCLUSIONS
  These results indicate that zinc remains inside the ENPP4 protein, a BCG activated tumoricidal macrophage protein, throughout the simulation. Important information for the design of new inhibitors was obtained.
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. dmyan@jlu.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yan
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Qianjin Street 2699#, Changchun City, Jilin Province, China. weiweihan@jlu.edu.cn.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Han
authors.affiliation: Intensive Care Unit, The Affiliated Hospital of Qingdao University, Jiangsu Road 16#, Qingdao, China. gonewithwind18@163.com.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. liuqihui4521141@163.com.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. jzjinzhengjz@163.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. 43775705@qq.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Chu
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. tianyuan_91@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. bupafengyu05@163.com.
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. 1175113240@qq.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. 624935095@qq.com.
authors.forename: Dunhuang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of basic Medical sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China. zxunzhux@vip.sohu.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D020134:Catalytic Domain; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D010802:Phylogeny; D011994:Recombinant Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D016415:Sequence Alignment; D012984:Software; D040681:Structural Homology, Protein; D013379:Substrate Specificity
chemical_list: D000906:Antibodies; D018076:DNA, Complementary; D011994:Recombinant Proteins; D010727:Phosphoric Diester Hydrolases
references.citation: J Biochem. 2010 Jul;148(1):13-24
references.pmid: 20495010
references.citation: Mol Cancer. 2015;14:203
references.pmid: 26607222
references.citation: Cell Cycle. 2009 Nov 15;8(22):3695-701
references.pmid: 19855166
references.citation: Cell Mol Immunol. 2007 Oct;4(5):359-67
references.pmid: 17976316
references.citation: Nat Struct Mol Biol. 2011 Feb;18(2):198-204
references.pmid: 21240271
references.citation: Front Endocrinol (Lausanne). 2015 Feb 02;6:12
references.pmid: 25699021
references.citation: Acta Neuropathol. 2012 Jul;124(1):99-110
references.pmid: 22311740
references.citation: J Immunol Methods. 2007 Apr 10;321(1-2):80-5
references.pmid: 17306824
references.citation: J Comput Chem. 2011 Mar;32(4):600-6
references.pmid: 20812321
references.citation: PLoS One. 2010;5(11):e15018
references.pmid: 21124899
references.citation: Cancer Res. 2002 Sep 1;62(17):5069-75
references.pmid: 12208763
references.citation: Eur J Pharmacol. 2009 Mar 15;606(1-3):17-24
references.pmid: 19374858
references.citation: Arterioscler Thromb Vasc Biol. 2012 Jan;32(1):24-32
references.pmid: 22015657
references.citation: Future Oncol. 2014 Jun;10(8):1443-56
references.pmid: 25052754
references.citation: J Comput Chem. 2010 Jan 30;31(2):455-61
references.pmid: 19499576
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16876-81
references.pmid: 23027977
references.citation: J Cell Biol. 2002 Jul 22;158(2):227-33
references.pmid: 12119361
references.citation: Scand J Immunol. 2007 Feb;65(2):148-57
references.pmid: 17257219
references.citation: Hepatology. 2014 May;59(5):2034-42
references.pmid: 24115204
references.citation: Diabetes. 2013 Oct;62(10):3553-60
references.pmid: 23835331
references.citation: Purinergic Signal. 2015 Dec;11(4):455-61
references.pmid: 26306905
references.citation: Adv Biol Regul. 2013 Jan;53(1):112-7
references.pmid: 23069371
references.citation: Oncol Rep. 2011 Sep;26(3):615-20
references.pmid: 21687955
references.citation: J Comput Aided Mol Des. 2010 May;24(5):417-22
references.pmid: 20401516
references.citation: PLoS One. 2010;5(10):e13571
references.pmid: 21042580
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W116-8
references.pmid: 16844972