2av0: Difference between revisions

Revision as of 17:31, 21 February 2008

F97L with CO bound

OverviewOverview

Residue F4 (Phe 97) undergoes the most dramatic ligand-linked transition in Scapharca dimeric hemoglobin, with its packing in the heme pocket in the unliganded (T) state suggested to be a primary determinant of its low affinity. Mutation of Phe 97 to Leu (previously reported), Val, and Tyr increases oxygen affinity from 8- to 100-fold over that of the wild type. The crystal structures of F97L and F97V show side chain packing in the heme pocket for both R and T state structures. In contrast, in the highest-affinity mutation, F97Y, the tyrosine side chain remains in the interface (high-affinity conformation) even in the unliganded state. Comparison of these mutations reveals a correlation between side chain packing in the heme pocket and oxygen affinity, indicating that greater mass in the heme pocket lowers oxygen affinity due to impaired movement of the heme iron into the heme plane. The results indicate that a key hydrogen bond, previously hypothesized to have a central role in regulation of oxygen affinity, plays at most only a small role in dictating ligand affinity. Equivalent mutations in sperm whale myoglobin alter ligand affinity by only 5-fold. The dramatically different responses to mutations at the F4 position result from subtle, but functionally critical, stereochemical differences. In myoglobin, an eclipsed orientation of the proximal His relative to the A and C pyrrole nitrogen atoms provides a significant barrier for high-affinity ligand binding. In contrast, the staggered orientation of the proximal histidine found in liganded HbI renders its ligand affinity much more susceptible to packing contacts between F4 and the heme group. These results highlight very different strategies used by cooperative hemoglobins in molluscs and mammals to control ligand affinity by modulation of the stereochemistry on the proximal side of the heme.

About this StructureAbout this Structure

2AV0 is a Single protein structure of sequence from Scapharca inaequivalvis with and as ligands. This structure supersedes the now removed PDB entry 3HBI. Full crystallographic information is available from OCA.

ReferenceReference

Residue F4 plays a key role in modulating oxygen affinity and cooperativity in Scapharca dimeric hemoglobin., Knapp JE, Bonham MA, Gibson QH, Nichols JC, Royer WE Jr, Biochemistry. 2005 Nov 8;44(44):14419-30. PMID:16262242

Page seeded by OCA on Thu Feb 21 16:31:16 2008

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OCA

@@ Line 1: / Line 1: @@
-[[Image:2av0.gif|left|200px]]<br />
+[[Image:2av0.gif|left|200px]]<br /><applet load="2av0" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2av0" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2av0, resolution 1.50&Aring;" />
 '''F97L with CO bound'''<br />
 ==Overview==
-Residue F4 (Phe 97) undergoes the most dramatic ligand-linked transition, in Scapharca dimeric hemoglobin, with its packing in the heme pocket in, the unliganded (T) state suggested to be a primary determinant of its low, affinity. Mutation of Phe 97 to Leu (previously reported), Val, and Tyr, increases oxygen affinity from 8- to 100-fold over that of the wild type., The crystal structures of F97L and F97V show side chain packing in the, heme pocket for both R and T state structures. In contrast, in the, highest-affinity mutation, F97Y, the tyrosine side chain remains in the, interface (high-affinity conformation) even in the unliganded state., Comparison of these mutations reveals a correlation between side chain, packing in the heme pocket and oxygen affinity, indicating that greater, mass in the heme pocket lowers oxygen affinity due to impaired movement of, the heme iron into the heme plane. The results indicate that a key, hydrogen bond, previously hypothesized to have a central role in, regulation of oxygen affinity, plays at most only a small role in, dictating ligand affinity. Equivalent mutations in sperm whale myoglobin, alter ligand affinity by only 5-fold. The dramatically different responses, to mutations at the F4 position result from subtle, but functionally, critical, stereochemical differences. In myoglobin, an eclipsed, orientation of the proximal His relative to the A and C pyrrole nitrogen, atoms provides a significant barrier for high-affinity ligand binding. In, contrast, the staggered orientation of the proximal histidine found in, liganded HbI renders its ligand affinity much more susceptible to packing, contacts between F4 and the heme group. These results highlight very, different strategies used by cooperative hemoglobins in molluscs and, mammals to control ligand affinity by modulation of the stereochemistry on, the proximal side of the heme.
+Residue F4 (Phe 97) undergoes the most dramatic ligand-linked transition in Scapharca dimeric hemoglobin, with its packing in the heme pocket in the unliganded (T) state suggested to be a primary determinant of its low affinity. Mutation of Phe 97 to Leu (previously reported), Val, and Tyr increases oxygen affinity from 8- to 100-fold over that of the wild type. The crystal structures of F97L and F97V show side chain packing in the heme pocket for both R and T state structures. In contrast, in the highest-affinity mutation, F97Y, the tyrosine side chain remains in the interface (high-affinity conformation) even in the unliganded state. Comparison of these mutations reveals a correlation between side chain packing in the heme pocket and oxygen affinity, indicating that greater mass in the heme pocket lowers oxygen affinity due to impaired movement of the heme iron into the heme plane. The results indicate that a key hydrogen bond, previously hypothesized to have a central role in regulation of oxygen affinity, plays at most only a small role in dictating ligand affinity. Equivalent mutations in sperm whale myoglobin alter ligand affinity by only 5-fold. The dramatically different responses to mutations at the F4 position result from subtle, but functionally critical, stereochemical differences. In myoglobin, an eclipsed orientation of the proximal His relative to the A and C pyrrole nitrogen atoms provides a significant barrier for high-affinity ligand binding. In contrast, the staggered orientation of the proximal histidine found in liganded HbI renders its ligand affinity much more susceptible to packing contacts between F4 and the heme group. These results highlight very different strategies used by cooperative hemoglobins in molluscs and mammals to control ligand affinity by modulation of the stereochemistry on the proximal side of the heme.
 ==About this Structure==
-AV0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Scapharca_inaequivalvis Scapharca inaequivalvis] with HEM and CMO as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 3HBI. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AV0 OCA].
+AV0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Scapharca_inaequivalvis Scapharca inaequivalvis] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=CMO:'>CMO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 3HBI. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AV0 OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Scapharca inaequivalvis]]
 [[Category: Single protein]]
-[[Category: Bonham, M.A.]]
+[[Category: Bonham, M A.]]
-[[Category: Gibson, Q.H.]]
+[[Category: Gibson, Q H.]]
-[[Category: Jr., W.E.Royer.]]
+[[Category: Jr., W E.Royer.]]
-[[Category: Knapp, J.E.]]
+[[Category: Knapp, J E.]]
-[[Category: Nichols, J.C.]]
+[[Category: Nichols, J C.]]
 [[Category: CMO]]
 [[Category: HEM]]
@@ Line 26: / Line 25: @@
 [[Category: oxygen transport]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 13:28:33 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:31:16 2008''