STRUCTURAL PREDICTION OF HUMAN ZIP 2 AND ZIP4 BASED ON HOMOLOGY MODELLING AND MOLECULAR SIMULATION

GITA SYAHPUTRA; NUNIK GUSTINI; MELVA LOUISA; MASTERIA YUNOVILSA PUTRA; ADILAH FADILAH

doi:10.22159/ijap.2023v15i5.48240

Authors

GITA SYAHPUTRA Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta-10430, Indonesia. Research Center for Vaccine and Drug, National Research and Innovation Agency, Cibinong-16911, Indonesia
NUNIK GUSTINI Research Center for Vaccine and Drug, National Research and Innovation Agency, Cibinong-16911, Indonesia https://orcid.org/0000-0001-6249-2424
MELVA LOUISA Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta-10430, Indonesia
MASTERIA YUNOVILSA PUTRA Research Center for Vaccine and Drug, National Research and Innovation Agency, Cibinong-16911, Indonesia
ADILAH FADILAH Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta-10430, Indonesia

DOI:

https://doi.org/10.22159/ijap.2023v15i5.48240

Keywords:

3D structure, Zinc transporter, Molecular modelling, Molecular docking, Structural biology

Abstract

Objective: This study aimed to analyze the structural proteins of zinc transporters as the target for drug actions and their molecular interactions.

Methods: The present study is about the homology modelling and analysis of the zinc transporter function using the in silico molecular modelling method. Homology modelling predicts the 3D structure of a protein based on the sequence alignment with one or more template proteins of known structure. This study using in silico molecular modelling method, explains the 3D structure of human ZIP 2 and ZIP4 with Ramachandran Plot analysis, physical and chemical characteristics, transmembrane prediction with structural biology, and binding site prediction through molecular docking simulation.

Results: Based on the physicochemical properties of the 3D structure of the ZIP2 and ZIP4 proteins, each comprises 309 amino acids and 582 amino acids with pI values of 5.85 and 5.24. The amino acid composition analysis showed that both proteins contain many Leucine amino acids. The Ramachandran diagram concludes that both proteins are stable in the stereochemical conformation forming a secondary structure. The binding amino acids on ZIP2 include Glu281, His216, Ser284, and Arg46. The binding amino acids in ZIP4 include Gln148, Gln154, Thr155, His197, Ala138, and Lys157.

Conclusion: Establishment of the structure and function of human ZIP2 and ZIP4 as zinc transporters in cell membranes and prediction of ZIP2 and ZIP4 binding sites through molecular dcoking.

Downloads

Download data is not yet available.

References

Whitehead MW, Thompson RPH, Powell JJ. Regulation of metal absorption in the gastrointestinal tract. Gut. 1996;39(5):625-8. doi: 10.1136/gut.39.5.625, PMID 9026473.

Lonnerdal B, Schneeman BO, Keen CL, Hurley LS. Molecular distribution of zinc in biliary and pancreatic secretions. Biol Trace Elem Res. 1980;2(3):149-58. doi: 10.1007/BF02785351, PMID 24271265.

Finley JW, Johnson PE, Reeves PG, Vanderpool RA, Briske Anderson M. Effect of bile/pancreatic secretions on absorption of radioactive or stable zinc. In vivo and in vitro studies. Biol Trace Elem Res. 1994;42(2):81-96. doi: 10.1007/BF02785381, PMID 7981007.

Kambe T, Taylor KM, Fu D. Zinc transporters and their functional integration in mammalian cells. J Biol Chem. 2021;296:(100320). doi: 10.1016/j.jbc.2021.100320, PMID 33485965.

Jeong J, Eide DJ. The SLC39 family of zinc transporters. Mol Aspects Med. 2013;34(2-3):612-9. doi: 10.1016/j.mam.2012.05.011, PMID 23506894.

Gaither LA, Eide DJ. The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J Biol Chem. 2001;276(25):22258-64. doi: 10.1074/jbc.M101772200, PMID 11301334.

Gaither LA, Eide DJ. Functional expression of the human hZIP2 zinc transporter. J Biol Chem. 2000;275(8):5560-4. doi: 10.1074/jbc.275.8.5560, PMID 10681536.

Hojyo S, Fukada T. Roles of zinc signaling in the immune system. J Immunol Res. 2016;2016:6762343. doi: 10.1155/2016/6762343, PMID 27872866.

Maret W. Zinc coordination environments in proteins as redox sensors and signal transducers. Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1419-41. doi: 10.1089/ars.2006.8.1419, PMID 16987000.

Andreini C, Banci L, Bertini I, Rosato A. Counting the zinc-proteins encoded in the human genome. J Proteome Res. 2006;5(1):196-201. doi: 10.1021/pr050361j, PMID 16396512.

Kimura T, Kambe T. The functions of metallothionein and ZIP and ZnT transporters: an overview and perspective. Int J Mol Sci. 2016;17(3):336. doi: 10.3390/ijms17030336, PMID 26959009.

Guo H, Yu Y, Hong Z, Zhang Y, Xie Q, Chen H. Effect of collagen peptide-chelated zinc nanoparticles from pufferfish skin on zinc bioavailability in rats. J Med Food. 2021;24(9):987-96. doi: 10.1089/jmf.2021.K.0038, PMID 34448624.

Kumar B, Praveen D, Chowdary PR, Aanandhi MV. A prospective single-blinded study on safety and efficacy of cholecalciferol supplementation in pulmonary tuberculosis. Drug Invent Today. 2019;12(11).

Kibenge F, McKibbon A, Kibenge M, Wang Y. Bioinformatics analysis identifies a small ORF in the genome of fish nidoviruses of genus oncotshavirus predicted to encode a novel integral protein. Microbiology Research. 2021;12(4):753-64. doi: 10.3390/microbiolres12040055.

Sanchez R, Sali A. Large-scale protein structure modeling of the Saccharomyces cerevisiae genome. Proc Natl Acad Sci USA. 1998;95(23):13597-602. doi: 10.1073/pnas.95.23.13597, PMID 9811845.

Arwansyah A, Arif AR, Syahputra G, Sukarti S, Kurniawan I. Theoretical studies of thiazolyl-pyrazoline derivatives as promising drugs against malaria by QSAR modelling combined with molecular docking and molecular dynamics simulation. Mol Simul. 2021;47(12):988-1001. doi: 10.1080/08927022.2021.1935926.

Nurhasanah N, Fadilah F, Bahtiar A. Prediction of active compounds of Muntingia calabura as a potential treatment for chronic obstructive pulmonary diseases by network pharmacology integrated with molecular docking. Int J Appl Pharm. 2023;15(1):274-9.

Sala D, Giachetti A, Rosato A. Insights into the dynamics of the human zinc transporter ZnT8 by MD simulations. J Chem Inf Model. 2021;61(2):901-12. doi: 10.1021/acs.jcim.0c01139, PMID 33508935.

Haraguichi H. Springrer. Metallom Integr Biometal Sci; 2017.

Mao X, Kim BE, Wang F, Eide DJ, Petris MJ. A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. J Biol Chem. 2007;282(10):6992-7000. doi: 10.1074/jbc.M610552200, PMID 17202136.

Hogstrand C, Kille P, Nicholson RI, Taylor KM. Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends Mol Med. 2009;15(3):101-11. doi: 10.1016/j.molmed.2009.01.004, PMID 19246244.

Kambe T, Weaver BP, Andrews GK. The genetics of essential metal homeostasis during development. Genesis. 2008;46(4):214-28. doi: 10.1002/dvg.20382, PMID 18395838.

Schmitt Ulms G, Ehsani S, Watts JC, Westaway D, Wille H. Evolutionary descent of prion genes from the ZIP family of metal Ion transporters. Plos One. 2009;4(9):e7208. doi: 10.1371/journal.pone.0007208, PMID 19784368.

Maywald M, Rink L. Zinc in human health and infectious diseases. Biomolecules. 2022;12(12):1-29. doi: 10.3390/biom12121748, PMID 36551176.

Udechukwu MC, Collins SA, Udenigwe CC. Prospects of enhancing dietary zinc bioavailability with food-derived zinc-chelating peptides. Food Funct. 2016 Oct;7(10):4137-44. doi: 10.1039/c6fo00706f, PMID 27713952.