Vanessa Chaplin/sandbox2: Difference between revisions
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The <scene name='40/400587/Active_site/8'>active site</scene>, which is located on a deep cleft between the β-strands comprising the DBSH core, contains the essential Fe(II). It is normally coordinated by the three Fe(II)-binding <scene name='40/400587/Active_site/14'>ligands</scene> formed by the conserved triad sequence, His-X-Asp/Glu-Xn-His.<ref name="review" /><ref>Schofield, C.J., Ratcliffe, P.J. "Signalling Bypoxia by HIF Hydroxylases." Biochemical and Biophysical Research Communications, August 24, 2005, 338, 617-626. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16139242 16139242]</ref><ref name="structure" /> , 2-OG (which in this scene is replaced by HG) and a water molecule to form an octahedral geometry. Aside from the triad motif residues and those that bind 2-OG, the residues that are predominant inside the active site are nonpolar in nature. This is evidence of the enzyme's need to protect the protein core from oxidation by reactive species that are sometimes generated from iron-related reactions such as Fenton chemistry.<ref name="structure" /> | The <scene name='40/400587/Active_site/8'>active site</scene>, which is located on a deep cleft between the β-strands comprising the DBSH core, contains the essential Fe(II). It is normally coordinated by the three Fe(II)-binding <scene name='40/400587/Active_site/14'>ligands</scene> formed by the conserved triad sequence, His-X-Asp/Glu-Xn-His.<ref name="review" /><ref>Schofield, C.J., Ratcliffe, P.J. "Signalling Bypoxia by HIF Hydroxylases." Biochemical and Biophysical Research Communications, August 24, 2005, 338, 617-626. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16139242 16139242]</ref><ref name="structure" /> , 2-OG (which in this scene is replaced by HG) and a water molecule to form an octahedral geometry. Aside from the triad motif residues and those that bind 2-OG, the residues that are predominant inside the active site are nonpolar in nature. This is evidence of the enzyme's need to protect the protein core from oxidation by reactive species that are sometimes generated from iron-related reactions such as Fenton chemistry.<ref name="structure" /> | ||
Upon binding of substrate, the <scene name='40/400587/B2b3_loop/2'>β2β3</scene> loop region of PHD2 undergoes a large conformational change (Figure 1). The β2β3 loop moves toward the active site and closes over the active site entrance. This loop movement is believed to be essential for the catalytic function of PHD2. The β2β3 loop region is mostly conserved in PHDs with minor differences. Mutational studies on the β2β3 loop region showed that this loop is significant for substrate recognition of PHDs<ref>PMID:18063574</ref>. | Upon binding of substrate, the <scene name='40/400587/B2b3_loop/2'>β2β3</scene> loop region of PHD2 undergoes a large <scene name='60/609795/B2b3_loop_with_cood/1'>conformational change</scene> (Figure 1). The β2β3 loop moves toward the active site and closes over the active site entrance. This loop movement is believed to be essential for the catalytic function of PHD2. The β2β3 loop region is mostly conserved in PHDs with minor differences. Mutational studies on the β2β3 loop region showed that this loop is significant for substrate recognition of PHDs<ref>PMID:18063574</ref>. | ||
[[Image:PHD2.png|315 px|thumb|Fig. 1: Substrate bound (purple) and unbound (green) PHD2. Figure created with PyMol. PDB IDs 2G19, 3HQR.]] | [[Image:PHD2.png|315 px|thumb|Fig. 1: Substrate bound (purple) and unbound (green) PHD2. Figure created with PyMol. PDB IDs 2G19, 3HQR.]] | ||
