This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2d5z
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2d5z.gif|left|200px]]<br /> | + | [[Image:2d5z.gif|left|200px]]<br /><applet load="2d5z" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2d5z" size=" | + | |
caption="2d5z, resolution 1.45Å" /> | caption="2d5z, resolution 1.45Å" /> | ||
'''Crystal structure of T-state human hemoglobin complexed with three L35 molecules'''<br /> | '''Crystal structure of T-state human hemoglobin complexed with three L35 molecules'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Although detailed crystal structures of haemoglobin (Hb) provide a clear | + | Although detailed crystal structures of haemoglobin (Hb) provide a clear understanding of the basic allosteric mechanism of the protein, and how this in turn controls oxygen affinity, recent experiments with artificial effector molecules have shown a far greater control of oxygen binding than with natural heterotropic effectors. Contrary to the established text-book view, these non-physiological compounds are able to reduce oxygen affinity very strongly without switching the protein to the T (tense) state. In an earlier paper we showed that bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb, strongly reducing the oxygen affinity of this protein conformation. Here we report the crystallisation of Hb with L35, a related compound, and show that this binds to the central cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen affinity is discussed, in relation to spectroscopic studies of effector binding. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2D5Z 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 HEM and L35 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2D5Z 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=HEM:'>HEM</scene> and <scene name='pdbligand=L35:'>L35</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D5Z OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Neya, S.]] | [[Category: Neya, S.]] | ||
| - | [[Category: Park, S | + | [[Category: Park, S Y.]] |
| - | [[Category: Tame, J | + | [[Category: Tame, J R.]] |
[[Category: Tsuneshige, A.]] | [[Category: Tsuneshige, A.]] | ||
[[Category: Yokoyama, T.]] | [[Category: Yokoyama, T.]] | ||
| Line 30: | Line 29: | ||
[[Category: l35]] | [[Category: l35]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:55:39 2008'' |
Revision as of 14:55, 21 February 2008
|
Crystal structure of T-state human hemoglobin complexed with three L35 molecules
Contents |
Overview
Although detailed crystal structures of haemoglobin (Hb) provide a clear understanding of the basic allosteric mechanism of the protein, and how this in turn controls oxygen affinity, recent experiments with artificial effector molecules have shown a far greater control of oxygen binding than with natural heterotropic effectors. Contrary to the established text-book view, these non-physiological compounds are able to reduce oxygen affinity very strongly without switching the protein to the T (tense) state. In an earlier paper we showed that bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb, strongly reducing the oxygen affinity of this protein conformation. Here we report the crystallisation of Hb with L35, a related compound, and show that this binds to the central cavity of both R and T state Hb. The mechanism by which L35 reduces oxygen affinity is discussed, in relation to spectroscopic studies of effector binding.
Disease
Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], Erythrocytosis OMIM:[141850], HPFH, deletion type OMIM:[141900], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Heinz body anemias, beta- OMIM:[141900], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia, alpha- OMIM:[141850], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, alpha- OMIM:[141800], Thalassemias, beta- OMIM:[141900]
About this Structure
2D5Z is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human and carbonmonoxy horse haemoglobin bound to the effector molecule L35., Yokoyama T, Neya S, Tsuneshige A, Yonetani T, Park SY, Tame JR, J Mol Biol. 2006 Feb 24;356(3):790-801. Epub 2005 Dec 21. PMID:16403522
Page seeded by OCA on Thu Feb 21 16:55:39 2008
