ArticleThe Journal of biological chemistry2011
Blocking the gate to ligand entry in human hemoglobin.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Direct observation of two-channel photodissociation of carbon monoxide from the hemoglobin subunits.Nature communications · 2025Article
- Ordered Motions in the Nitric-Oxide Dioxygenase Mechanism of Flavohemoglobin and Assorted Globins with Tightly Coupled Reductases.Advances in experimental medicine and biology · 2023Article
- Kinetic mechanisms for OMolecular aspects of medicine · 2022Review
- Direct observation of ligand migration within human hemoglobin at work.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Lessons Learned from 50 Years of Hemoglobin Research: Unstirred and Cell-Free Layers, Electrostatics, Baseball Gloves, and Molten Globules.Antioxidants & redox signaling · 2020Review
- Hemoglobin: Structure, Function and Allostery.Sub-cellular biochemistry · 2020Review
- Synthetic Fe/Cu Complexes: Toward Understanding Heme-Copper Oxidase Structure and Function.Chemical reviews · 2018Review
- Exploring the entry route of palmitic acid and palmitoylcarnitine into myoglobin.Archives of biochemistry and biophysics · 2018Article
- Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice.PloS one · 2017Article
- Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Post-translational transformation of methionine to aspartate is catalyzed by heme iron and driven by peroxide: a novel subunit-specific mechanism in hemoglobin.The Journal of biological chemistry · 2014Article
- A model for the flexibility of the distal histidine in dehaloperoxidase-hemoglobin A based on X-ray crystal structures of the carbon monoxide adduct.Biochemistry · 2014Article
- Autoxidation and oxygen binding properties of recombinant hemoglobins with substitutions at the αVal-62 or βVal-67 position of the distal heme pocket.The Journal of biological chemistry · 2013Article
- Development of recombinant hemoglobin-based oxygen carriers.Antioxidants & redox signaling · 2013Review
- Hydrophobic effect drives oxygen uptake in myoglobin via histidine E7.The Journal of biological chemistry · 2013Article
- Determination of ligand pathways in globins: apolar tunnels versus polar gates.The Journal of biological chemistry · 2012Article
- Quaternary structure controls ligand dynamics in soluble guanylate cyclase.The Journal of biological chemistry · 2012Article
- An atomistic view on human hemoglobin carbon monoxide migration processes.Biophysical journal · 2012Article
- Biophysical Properties of Lumbricus terrestris Erythrocruorin and Its Potential Use as a Red Blood Cell Substitute.Journal of functional biomaterials · 2012Article
- Structures and oxygen affinities of crystalline human hemoglobin C (β6 Glu->Lys) in the R and R2 quaternary structures.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
His(E7) to Trp replacements in HbA lead to markedly biphasic bimolecular CO rebinding after laser photolysis. For isolated mutant subunits, the fraction of fast phase increases with increasing [CO], suggesting a competition between binding to an open conformation with an empty E7 channel and relaxation to blocked or closed, slowly reacting states. The rate of conformational relaxation of the open state is ∼18,000 s(-1) in α subunits and ∼10-fold faster in β subunits, ∼175,000 s(-1). Crystal structures were determined for tetrameric α(WT)β(Trp-63) HbCO, α(Trp-58)β(WT) deoxyHb, and Trp-64 deoxy- and CO-Mb as controls. In Trp-63(E7) βCO, the indole side chain is located in the solvent interface, blocking entry into the E7 channel. Similar blocked Trp-64(E7) conformations are observed in the mutant Mb crystal structures. In Trp-58(E7) deoxy-α subunits, the indole side chain fills both the channel and the distal pocket, forming a completely closed state. The bimolecular rate constant for CO binding, k'(CO), to the open conformations of both mutant Hb subunits is ∼80-90 μm(-1) s(-1), whereas k'(CO) for the completely closed states is 1000-fold slower, ∼0.08 μm(-1) s(-1). A transient intermediate with k'(CO) ≈ 0.7 μm(-1) s(-1) is observed after photolysis of Trp-63(E7) βCO subunits and indicates that the indole ring blocks the entrance to the E7 channel, as observed in the crystal structures of Trp(E7) deoxyMb and βCO subunits. Thus, either blocking or completely filling the E7 channel dramatically slows bimolecular binding, providing strong evidence that the E7 channel is the major pathway (≥90%) for ligand entry in human hemoglobin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.