1os3
From Proteopedia
(New page: 200px<br /> <applet load="1os3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1os3, resolution 1.95Å" /> '''Dehydrated T6 human...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1os3.gif|left|200px]]<br /> | + | [[Image:1os3.gif|left|200px]]<br /><applet load="1os3" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1os3" size=" | + | |
caption="1os3, resolution 1.95Å" /> | caption="1os3, resolution 1.95Å" /> | ||
'''Dehydrated T6 human insulin at 100 K'''<br /> | '''Dehydrated T6 human insulin at 100 K'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of the T(6) hexameric form of human insulin has been | + | The structure of the T(6) hexameric form of human insulin has been determined at both room temperature and 100 K from a single air-dried crystal. At 100 K, the space group is R3 and the asymmetric unit consists of a dimer, as has been observed previously in hydrated structures. At room temperature, the space group is P1 and the unit cell contains a quasi-threefold-symmetric hexamer. In the absence of stabilizing water interactions, the N-termini of all six A chains in the room-temperature structure appear to have undergone partial unfolding, but the N-termini of these chains are well ordered in the 100 K structure. Other differences between the room-temperature and 100 K structures involve the coordination around the zinc ions. At 100 K, both zinc ions clearly exhibit dual coordination: zinc is octahedrally coordinated in one half of the zinc sites but tetrahedrally coordinated in the other half; at room temperature, the electron densities suggest tetrahedral coordination but the bond distances to the fourth ligands are longer than expected. Contrary to what has been observed to date in all other T(6) insulin structures, there are no contacts between pairs of GluB13 residues, either at room temperature or at 100 K, that would suggest the presence of a hydrogen bond. At room temperature, three of the six independent GluB13 side chains are disordered; at 100 K, both independent side chains are disordered. The disorder in the GluB13 side chains and the lack of contacts between carboxylate groups suggests that as a result of disruption of the hydration structure in the central core of the hexamer, all six B13 carboxylates bear a negative charge. This in turn suggests that in the hydrated structures the well ordered water structure in the central core is involved in stabilizing the B13 side-chain conformations and modulating charge repulsions among the six B13 glutamates if they are not protonated, or that, as is considered more likely, the water structure plays an important role in modulating the pK(a) values of the B13 glutamates, resulting in protonation and hydrogen-bond formation. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1OS3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1OS3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OS3 OCA]. |
==Reference== | ==Reference== | ||
| Line 17: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Blessing, R | + | [[Category: Blessing, R H.]] |
| - | [[Category: Smith, G | + | [[Category: Smith, G D.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
| Line 24: | Line 23: | ||
[[Category: data measured at 100 k]] | [[Category: data measured at 100 k]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:20:56 2008'' |
Revision as of 12:20, 21 February 2008
|
Dehydrated T6 human insulin at 100 K
Contents |
Overview
The structure of the T(6) hexameric form of human insulin has been determined at both room temperature and 100 K from a single air-dried crystal. At 100 K, the space group is R3 and the asymmetric unit consists of a dimer, as has been observed previously in hydrated structures. At room temperature, the space group is P1 and the unit cell contains a quasi-threefold-symmetric hexamer. In the absence of stabilizing water interactions, the N-termini of all six A chains in the room-temperature structure appear to have undergone partial unfolding, but the N-termini of these chains are well ordered in the 100 K structure. Other differences between the room-temperature and 100 K structures involve the coordination around the zinc ions. At 100 K, both zinc ions clearly exhibit dual coordination: zinc is octahedrally coordinated in one half of the zinc sites but tetrahedrally coordinated in the other half; at room temperature, the electron densities suggest tetrahedral coordination but the bond distances to the fourth ligands are longer than expected. Contrary to what has been observed to date in all other T(6) insulin structures, there are no contacts between pairs of GluB13 residues, either at room temperature or at 100 K, that would suggest the presence of a hydrogen bond. At room temperature, three of the six independent GluB13 side chains are disordered; at 100 K, both independent side chains are disordered. The disorder in the GluB13 side chains and the lack of contacts between carboxylate groups suggests that as a result of disruption of the hydration structure in the central core of the hexamer, all six B13 carboxylates bear a negative charge. This in turn suggests that in the hydrated structures the well ordered water structure in the central core is involved in stabilizing the B13 side-chain conformations and modulating charge repulsions among the six B13 glutamates if they are not protonated, or that, as is considered more likely, the water structure plays an important role in modulating the pK(a) values of the B13 glutamates, resulting in protonation and hydrogen-bond formation.
Disease
Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]
About this Structure
1OS3 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Lessons from an aged, dried crystal of T(6) human insulin., Smith GD, Blessing RH, Acta Crystallogr D Biol Crystallogr. 2003 Aug;59(Pt 8):1384-94. Epub 2003, Jul 23. PMID:12876340
Page seeded by OCA on Thu Feb 21 14:20:56 2008
