Sandbox Reserved 1739

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models PDB ID 2obq Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

This Sandbox is Reserved from August 30, 2022 through May 31, 2023 for use in the course Biochemistry I taught by Kimberly Lane at the Radford University, Radford, VA, USA. This reservation includes Sandbox Reserved 1730 through Sandbox Reserved 1749.

To get started: Click the edit this page tab at the top. Click on Show preview and then Save the page after each step, then edit it again. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

Contents 1 Hepatitis C Helicase/Primase 2 Function 3 Disease 4 Relevance 5 Structural highlights 6 References

Hepatitis C Helicase/Primase

Function

The function of Hepatitis C primase is to build the viral capsid. The viral capsid and two glycoproteins make up the genome (1). The function of Hepatitis C helicase is to stop viral RNA from binding by stripping it of its proteins. It is necessary for viral replication (2). Helicase can process a wide range of nucleic acid sequences and unwind them (5). Together, Hepatitis C primase and helicase functions together are still undetermined.

Disease

Hepatitis C (HCV) is a viral infection that causes inflammation of the liver. As of 2022 there has been no vaccine created for Hepatitis C (6).

Relevance

The relevance of Hepatitis C helicase/primase is that the helicase/protease combination in HCV is believed to play a pivotal role in the replication cycle of HCV. The helicase exists as a dimer, bearing mutations, and can be found in three different functional states (9). The three functional states include a substrate-unbound state, an ATP-bound state, and an NA-bound state. The presence of ATP transitions the protease from high NA binding affinity to low NA binding affinity. The cooperation of helicase/protease binding the DNA is affected by the length of the ss lattice, and the desired ss DNA length is around 22nt (3).

Structural highlights

2OBQ: for Hepatisis primase Method: X-Ray Diffraction. Resolution: 2.50 Å. Classification: Viral Protein. Organism(s): Hepacivirus C. Expression System: Escherichia coli. Deposited: 2006-12-19. Released: 2007-07-31. Deposition Author(s): Prongay, A.J., Guo, Z., Yao, N., Fischmann, T., Strickland, C., Myers Jr., J., Weber, P.C., Malcolm, B., Beyer, B.M., Ingram, R., Pichardo, J., Hong, Z., Prosise, W.W., Ramanathan, L., Taremi, S.S., Yarosh-Tomaine, T., Zhang, R., Senior, M., Yang, R., Arasappan, A., Bennett, F., Bogen, S.F., Chen, K., Jao, E., Liu, Y., Love, R.G., Saksena, A.K., Venkatraman, S., Girijavallabhan, V., Njoroge, F.G., Madison, V. Primary Structure: 180 amino acids. Secondary Structure (what types of secondary structure in the protein and number of each): Tertiary Structure:3 domains; domain 2 is linked to domains 1 and 3 by flexible linkers. 6 motifs; Walker A motif, the Phe loop, the Arg-clamp motif Quaternary Structure(number of subunits, quaternary structure name, quaternary symmetry):

8OHM for Hepatitis helicase: Method: X-Ray Diffraction. Resolution: 2.30 Å. Classification: Helicase. Organism(s): Hepacivirus C. Expression System: Escherichia coli BL21(DE3). Deposited: 1998-03-13. Released: 1999-04-20. Deposition Author(s): Cho, H.S., Ha, N.C., Kang, L.W., Oh, B.H. Primary Structure: 620 amino acids. Secondary Structure (what types of secondary structure in the protein and number of each): Beta sheets sandwiched between Alpha helices. Tertiary Structure(motif(s) present, domains): Quaternary Structure(number of subunits, quaternary structure name, quaternary symmetry):

References

[1]Gawlik, K.; Gallay, P. A. HCV Core Protein and Virus Assembly: What We Know without Structures. Immunologic research 2014, 60 (1), 1–10.

[2]Kolykhalov, A. A.; Mihalik, K.; Feinstone, S. M.; Rice, C. M. Hepatitis c Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3′ Nontranslated Region Are Essential for Virus Replication in Vivo. Journal of Virology 2000, 74 (4), 2046–2051.

[3]Donmez, I.; Rajagopal, V.; Jeong, Y.-J.; Patel, S. S. Nucleic Acid Unwinding by Hepatitis c Virus and Bacteriophage T7 Helicases Is Sensitive to Base Pair Stability. Journal of Biological Chemistry 2007, 282 (29), 21116–21123.

[4]Turkington, C. Hepatitis C; McGraw-Hill/Contemporary, 1998.

[5]Rajagopal, V.; Gurjar, M.; Levin, M. K.; Patel, S. S. The Protease Domain Increases the Translocation Stepping Efficiency of the Hepatitis c Virus NS3-4A Helicase. Journal of Biological Chemistry 2010, 285 (23), 17821–17832.

[6]Locatelli, G. A.; Spadari, S.; Maga, G. Hepatitis c Virus NS3 ATPase/Helicase: An ATP Switch Regulates the Cooperativity among the Different Substrate Binding Sites†. Biochemistry 2002, 41 (32), 10332–10342.