Journal:Acta Cryst D:S2059798319011355
From Proteopedia
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The structures of M-PMV PR contain an unusual water molecule buried deep in the active site structure, hydrogen-bonded in a tetrahedral fashion between the two active-site loops of the dimer, with the G28 N-H groups acting as donors and the side-chain O atoms of the N26 residues acting as acceptors. This water molecule is different from the nucleophilic molecule found in the active site of active aspartic proteases or from the one found at the inhibitor-flap interface of inhibitor complexes of retropepsins. Such a coordination of a water molecule has not been seen in any (retro)pepsin structures before. The side chains of the N26 residues take part in a wider H-bond network with water molecules coordinated also by V31 and L92. A similar pattern can be partially found in HIV-1 PR ([[5kr1]], [[1n49]]). In the apo structure of the protein ([[6s1w]]), one of the flaps (long loops gating access to the active site) is curled into the binding pocket and very well defined in the electron density, while the electron density of the other flap loop is invisible. While flap disorder is not surprising in apo structures of reropepsins, the perfect order of the other flap is an unusual feature, confirming again the unusual structural properties of the M-PMV enzyme. Also intriguingly, the tips of all the flap loops in the inhibitor complexes ([[6s1v]], [[6s1u]]) are disordered and not present in the electron density, although their visible stems seem to trace the direction found in inhibitor complexes of other dimeric retropepsins. The C/A mutations (C7A, C106A) have no effect on the M-PMV PR structure. | The structures of M-PMV PR contain an unusual water molecule buried deep in the active site structure, hydrogen-bonded in a tetrahedral fashion between the two active-site loops of the dimer, with the G28 N-H groups acting as donors and the side-chain O atoms of the N26 residues acting as acceptors. This water molecule is different from the nucleophilic molecule found in the active site of active aspartic proteases or from the one found at the inhibitor-flap interface of inhibitor complexes of retropepsins. Such a coordination of a water molecule has not been seen in any (retro)pepsin structures before. The side chains of the N26 residues take part in a wider H-bond network with water molecules coordinated also by V31 and L92. A similar pattern can be partially found in HIV-1 PR ([[5kr1]], [[1n49]]). In the apo structure of the protein ([[6s1w]]), one of the flaps (long loops gating access to the active site) is curled into the binding pocket and very well defined in the electron density, while the electron density of the other flap loop is invisible. While flap disorder is not surprising in apo structures of reropepsins, the perfect order of the other flap is an unusual feature, confirming again the unusual structural properties of the M-PMV enzyme. Also intriguingly, the tips of all the flap loops in the inhibitor complexes ([[6s1v]], [[6s1u]]) are disordered and not present in the electron density, although their visible stems seem to trace the direction found in inhibitor complexes of other dimeric retropepsins. The C/A mutations (C7A, C106A) have no effect on the M-PMV PR structure. | ||
| - | + | <scene name='82/824514/Cv/3'>The catalytic loops of 3MI (6s1u) with a water molecule</scene>. | |
<b>References</b><br> | <b>References</b><br> | ||
<references/> | <references/> | ||
</StructureSection> | </StructureSection> | ||
__NOEDITSECTION__ | __NOEDITSECTION__ | ||
Revision as of 13:00, 8 September 2019
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
