Journal:Acta Cryst F:S2053230X20011309
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| - | <StructureSection load='' size='450' side='right' scene=' | + | <StructureSection load='' size='450' side='right' scene='85/859611/Cv/1' caption=''> |
===Multiple crystal forms of human MacroD2=== | ===Multiple crystal forms of human MacroD2=== | ||
<big>Sarah Wazir, Mirko M. Maksimainen and Lari Lehtiö</big> <ref>doi 10.1107/S2053230X20011309</ref> | <big>Sarah Wazir, Mirko M. Maksimainen and Lari Lehtiö</big> <ref>doi 10.1107/S2053230X20011309</ref> | ||
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
MacroD2 is one of the three human macrodomain proteins characterized for their protein linked mono-ADP-ribosyl-hydrolyzing activity. MacroD2 is a single domain protein containing a deep ADP-ribose binding groove. In this study new crystallization conditions for MacroD2 were found and three crystal structures of human MacroD2 in apo state were solved in space groups P4<sub>1</sub>2<sub>1</sub>2, P4<sub>3</sub>2<sub>1</sub>2 and P4<sub>3</sub> and refined at 1.75, 1.90 and 1.70 Å resolutions, respectively. Structural comparison of the apo crystal structures to the previously reported MacroD2 crystal structure in complex with ADP-ribose revealed conformational changes in the side chains of Val101, Ile189 and Phe224 induced by the binding of ADP-ribose into the active site. These conformational variations may potentially facilitate design efforts of a MacroD2 inhibitor. | MacroD2 is one of the three human macrodomain proteins characterized for their protein linked mono-ADP-ribosyl-hydrolyzing activity. MacroD2 is a single domain protein containing a deep ADP-ribose binding groove. In this study new crystallization conditions for MacroD2 were found and three crystal structures of human MacroD2 in apo state were solved in space groups P4<sub>1</sub>2<sub>1</sub>2, P4<sub>3</sub>2<sub>1</sub>2 and P4<sub>3</sub> and refined at 1.75, 1.90 and 1.70 Å resolutions, respectively. Structural comparison of the apo crystal structures to the previously reported MacroD2 crystal structure in complex with ADP-ribose revealed conformational changes in the side chains of Val101, Ile189 and Phe224 induced by the binding of ADP-ribose into the active site. These conformational variations may potentially facilitate design efforts of a MacroD2 inhibitor. | ||
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| + | Ribbon representations of the secondary structures of apo MacroD2 in: | ||
| + | *<scene name='85/859611/Cv/4'>P41212</scene> (PDB ID [[6y4y]], chain A) (light blue). | ||
| + | *<scene name='85/859611/Cv/3'>P43212</scene> (PDB ID [[6y4z]], chain A) (warm pink). | ||
| + | *<scene name='85/859611/Cv/6'>P43</scene> (PDB ID [[6y73]], chain A) (salmon). | ||
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| + | <scene name='85/859611/Cv/7'>Ribbon representation of the superimposed crystal forms of MacroD2</scene>. Secondary structures of P4<sub>1</sub>2<sub>1</sub>2 (PDB ID [[6y4y]]), P4<sub>3</sub>2<sub>1</sub>2 (PDB ID [[6y4z]]), and P4<sub>3</sub> (PDB ID [[6y73]]) are coloured as light blue, warm pink and salmon, respectively. | ||
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| + | <scene name='85/859611/Cv/21'>Superimposition of MacroD2 crystal structures</scene>: MacroD2-ADPr complex structure (PDB ID [[4iqy]]; (orange) and ligand-free MacroD2 (PDB ID [[6y4y]]) (light blue). ADPr and its surrounding residues are shown as sticks. The labelled residues are important for the catalytic activity of the enzyme. The hydrogen bonds are presented as dash lines. Wa is the catalytic water molecule in MacroD2-ADPr complex. | ||
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| + | Crystal structure comparison of MacroD2 (PDB ID [[6y4y]]) and MacroD1 (PDB ID [[2x47]]) catalytic fragments showing their mono-ADP-ribosyl-hydrolase functions: | ||
| + | *<scene name='85/859611/Cv/22'>Overall view of the superimposition of apo MacroD2 and MacroD1</scene>. MacroD2 structure (light blue), ligand-free MacroD1 (cyan). The ADPr of the MacroD2-ADPr structure is coloured in orange (PDB ID [[4iqy]]). | ||
| + | *<scene name='85/859611/Cv/25'>The conformational difference of the loop 2 between MacroD1 and MacroD2</scene>. ADPr and its surrounding residues are shown as sticks. The labelled residues are important for the catalytic activities of these enzymes. | ||
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| + | '''PDB references:''' The crystal structure of human MACROD2 in space group P41212, [[6y4y]]; The crystal structure of human MACROD2 in space group P43212, [[6y4z]]; The crystal structure of human MACROD2 in space group P43, [[6y73]]. | ||
<b>References</b><br> | <b>References</b><br> | ||
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