Sandbox Reserved 774: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Michael B. Goshe, Shiva Akhlaghi

@@ Line 1: / Line 1: @@
 <!-- PLEASE DO NOT DELETE THIS TEMPLATE -->
-{{User:Michael_B._Goshe/Template_BCH455_555}}
+{{User:Michael_B._Goshe/Template_BCH455_555}}<Structure load='1QSO' size='350' frame='true' align='right' caption='3D Model of Hpa2. Clicking links in the test will highlighted : chains A,B,C,D, β-sheets, main chain, side chain, and residues 100-104.' scene='Insert optional scene name here' />
+=Histone Acetyltransferase Hpa2=
 <!-- PLEASE ADD YOUR CONTENT BELOW HERE -->
-<Structure load='1QSO' size='350' frame='true' align='right' caption='3D Model of Hpa2, showing: chains A,B,C,D, β-sheets, main chain, side chain, and residues 100-104.' scene='Insert optional scene name here' />
-=Histone Acetyltransferase Hpa2=
 Histone Acetyltransferase Hpa2 is a member of the GNAT (Gcn5-related N-acetyltransferases) super-family of enzymes that are found spread out across nature and use acyl-CoA's to acylate their cognate substrates.<ref name=desperate>"Histone Acetyltransferase HPA2 from Saccharomyces Cerevisiae." Protein Data Bank. EMDataBank, n.d. Web. 17 Nov. 2013.[http://www.rcsb.org/pdb/explore/explore.do?structureId=1QSO RCSB.org]</ref> GNAT is a catalytic subunit of ADA and SAGA histone acetyltransferase complexes. <ref>"GCN5/YGR252W Summary." YeastGenome.org. Standford University, n.d. Web. 26 Nov. 2013. [http://www.yeastgenome.org/cgi-bin/locus.fpl?locus=gcn5 YeastGenome.org]</ref>Hpa2 is found in the organism Saccharomyces Cerevisiae, which is more commonly known as Baker's Yeast.<ref>"Q06592 (HPA2_YEAST) Reviewed, UniProtKB/Swiss-Prot." Unitprot.org. UniProtKB, 13 Nov. 2013. Web. 16 Nov. 2013.[http://www.uniprot.org/uniprot/Q06592 UnitPro.org]</ref> It was also discovered in other organisms, such as Pelagibacterium halotolerans B2 - a marine halotolerant bacterium in the East China Sea. <ref>Huo. "Complete Genome Sequence of Pelagibacterium Halotolerans B2(T)." J. Bacteriol 197.8 (2012): 1. Web. 26 Nov. 2013. [http://www.ncbi.nlm.nih.gov/pubmed/22156395 NCBI.nlm.nih.gov]</ref> In vitro, Hpa2 serves to acetylate histone H3 'Lys-4' and 'Lys-14' and histone H4 'Lys-5' and 'Lys-12.' The acetylation of the e-amino group of lysines on the histone N terminal tails and core regions cause changes in the chromatin structure and dynamics, which often times leads to transcriptional activation.<ref>Sampath, el al. "Enzymology: Biochemical Characterization of Hpa2 and Hpa3-two Small Closely Related Acetyltransferases from S. Cerevisiae." Journal of Biological Chemistry (2013): 2-17. Web. 17 Nov. 2013. [http://www.jbc.org/content/early/2013/06/17/jbc.M113.486274.full.pdf JBC.org]</ref> In solution, Hpa2 forms a dimer, and upon binding with AcCoA forms a tetramer.<ref name=desperate/><ref name=Shiva/> It is classified as a [[transferase]].<ref name=Shiva>Angus-Hill, et al. "Crystal Structure of the Histone Acetyltransferase Hpa2: a Tetrameric Member of the Gcn5-related N-acetyltransferase Superfamily." J. Mol. Biol. 1999.3338 (1999): 1-14. Web. 18 Nov. 2013.</ref>
@@ Line 12: / Line 8: @@
 Has a four chain structure (<scene name='56/564050/Chain_a/1' target=0>A</scene>, <scene name='56/564050/Chain_b/1' target=0>B</scene>, <scene name='56/564050/Chain_c/1' target=0>C</scene>, <scene name='56/564050/Chain_d/1' target=0>D</scene>) with 2.4 Å resolution, and 2.9 Å resolution with a co-factor (acetyl-CoA). Core fold features include four conserved sequence motifs of the GNAT family, and comprises a central, highly curved five stranded <scene name='56/564050/Beta_sheets/1' target=0>β-sheet</scene> surrounded on both sides by helical segments.<ref name=Shiva/>
-Each monomer has a similar and compact α-β structure. The structure's core contains a central mixed five-stranded sheet structure from sheets β1 to β5. Strands β1 to β4, however, are organized in an anti-parallel arrangement while β4 and β5 are parallel, but only at their amino-terminal ends. At the other end of the parallel β4 and β5 strands, they are spread apart because of a β bulge in strand β4 caused by residue N74 of strand β3 as well as N91 and D92 of β4. The central sheet is accompanied on each side by two α-helices. Helices α1 and α2 are on one side of the sheet with α1 lying nearly flat against and perpendicular to the other direction of the strands, while helices α3 and α4 are on the opposite side of the sheet with helix α3 cupped within the curved face of the sheet. <ref name=Shiva/> The method used to determine the structure was [[X-ray crystallography]]. Sedimentation and crystal structure analysis clearly shows that Hpa2 is dimeric in solution and tetramerizes in the unit crystal. The crystal structure of the oligomer reveals that two Hpa2 dimers are held together by interaction between the bound acetyl-CoA molecules. The average B-factor value of the <scene name='56/564050/Bakhbone_mainechain/1' target=0>main chain</scene> is 23.9  with a 25.4 <scene name='56/564050/Sidechain/2' target=0>side chain</scene>. The R-factor is 0.19. <ref name=Shiva/>
+Each monomer has a similar and compact α-β structure. The structure's core contains a central mixed five-stranded sheet structure from sheets β1 to β5. Strands β1 to β4, however, are organized in an anti-parallel arrangement while β4 and β5 are parallel, but only at their amino-terminal ends. At the other end of the parallel β4 and β5 strands, they are spread apart because of a β bulge in strand β4 caused by residue N74 of strand β3 as well as N91 and D92 of β4. The central sheet is accompanied on each side by two α-helices. Helices α1 and α2 are on one side of the sheet with α1 lying nearly flat against and perpendicular to the other direction of the strands, while helices α3 and α4 are on the opposite side of the sheet with helix α3 cupped within the curved face of the sheet. <ref name=Shiva/> The method used to determine the structure was [[X-ray crystallography]]. Sedimentation and crystal structure analysis clearly shows that Hpa2 is dimeric in solution and tetramerizes in the unit crystal. The crystal structure of the oligomer reveals that two Hpa2 dimers are held together by interaction between the bound acetyl-CoA molecules. The average B-factor value of the <scene name='56/564050/Bakhbone_mainechain/1' target=0>main chain</scene> is 23.9  with a 25.4 <scene name='56/564050/Sidechain/2' target=0>side chain</scene>. The R-factor is 0.19. <ref name=Shiva/> [[Image:Chain.jpg.png | thumb | '''Figure 1.''' Sequence of Hpa2.]]
-[[Image:Chain.jpg.png | thumb | '''Figure 1.''' Sequence of Hpa2.]]
 ==Co-factor==
@@ Line 23: / Line 18: @@
 ==Active Site==
-The region around the <scene name='56/564050/Active_sites_zoom/1' target=1>active site</scene> has potential consequences for substrate binding. For Hpa2, there exists a pocket adjacent to the active site which is sealed off on two sides by the second Hpa2 monomer in each dimer. This pocket restricts the conformation of a polypeptide backbone in the vicinity of the active site. Therefore, Hpa2 is able to distinguish between potential substrate, whereby the only lysine side-chains that may enter the active site are those with surrounding polypeptides that can adopt a conformation with the ability to fit through the pocket. <ref name=Shiva/>
+The region around the <scene name='56/564050/Active_sites_zoom/1' target=1>active site</scene> has potential consequences for substrate binding. For Hpa2, there exists a pocket adjacent to the active site which is sealed off on two sides by the second Hpa2 monomer in each dimer. This pocket restricts the conformation of a polypeptide backbone in the vicinity of the active site. Therefore, Hpa2 is able to distinguish between potential substrate, whereby the only lysine side-chains that may enter the active site are those with surrounding polypeptides that can adopt a conformation with the ability to fit through the pocket. <ref name=Shiva/> <Structure load='1QSM' size='350' frame='true' align='right' caption='Hpa2 + AcCoA, showing: co-factor, backbone, β-strands, active site, α-helices.' scene='Insert optional scene name here' />
-<Structure load='1QSM' size='350' frame='true' align='right' caption='Hpa2 + AcCoA, showing: co-factor, backbone, β-strands, active site, α-helices.' scene='Insert optional scene name here' />