Hydrogen bond dynamics in the active site of photoactive yellow protein

Sigala, Paul A.; Tsuchida, Mark A.; Herschlag, Daniel

doi:10.1073/pnas.0900168106

Cited by 78 publications

(172 citation statements)

References 48 publications

(67 reference statements)

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“…rsif.royalsocietypublishing.org J. R. Soc. Interface 11: 20130518 than the value of 15.2 ppm obtained from the NMR studies [49]. Hence, the H atom positions obtained in the neutron diffraction study [39] resulted in an overestimation of the chemical shift for O Glu46 -O pCA , and an underestimation of that for O Tyr42 -O pCA .…”

Section: H For Photoactive Yellow Proteinmentioning

confidence: 67%

“…The maximum d H value of approximately 20 ppm was observed near the centre of O Glu46 -O pCA [38]. The d H of approximately 15 ppm that was obtained from solution 1 H NMR studies of PYP [49] could not be obtained near to the centre of O Glu46 -O pCA , but only at the Glu46 or pCA moieties [38].…”

Section: H For Photoactive Yellow Proteinmentioning

confidence: 98%

“…Using the QM/MM optimized geometry, we calculated the d H value for the O Glu46 -O pCA bond and found it to be 14.5 ppm (PDB, 2ZOH [39]) or 14.6 ppm (PDB, 1OTB [50]) [38]; these values differ by 0.6-0.7 ppm from the experimental values of 15.2 ppm [49]. This discrepancy may also reflect the distribution of H-bond lengths, even in these high-resolution (approx.…”

Section: H For Photoactive Yellow Proteinmentioning

confidence: 99%

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Proton transfer reactions and hydrogen-bond networks in protein environments

Ishikita

Saito

2014

J. R. Soc. Interface.

172

169

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In protein environments, proton transfer reactions occur along polar or charged residues and isolated water molecules. These species consist of H-bond networks that serve as proton transfer pathways; therefore, thorough understanding of H-bond energetics is essential when investigating proton transfer reactions in protein environments. When the pK a values (or proton affinity) of the H-bond donor and acceptor moieties are equal, significantly short, symmetric H-bonds can be formed between the two, and proton transfer reactions can occur in an efficient manner. However, such short, symmetric H-bonds are not necessarily stable when they are situated near the protein bulk surface, because the condition of matching pK a values is opposite to that required for the formation of strong salt bridges, which play a key role in protein-protein interactions. To satisfy the pK a matching condition and allow for proton transfer reactions, proteins often adjust the pK a via electron transfer reactions or H-bond pattern changes. In particular, when a symmetric H-bond is formed near the protein bulk surface as a result of one of these phenomena, its instability often results in breakage, leading to large changes in protein conformation.

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Section: H For Photoactive Yellow Proteinmentioning

confidence: 67%

Section: H For Photoactive Yellow Proteinmentioning

confidence: 98%

Section: H For Photoactive Yellow Proteinmentioning

confidence: 99%

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Proton transfer reactions and hydrogen-bond networks in protein environments

Ishikita

Saito

2014

J. R. Soc. Interface.

172

169

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“…Hydrogen bonds are typically probed in a coarse fashion by ablating them via site-directed mutagenesis and evaluating the functional consequence of their removal. Although this approach can highlight their general functional importance, it does not reveal the physical properties of the intact hydrogen bonds that underpin their functional roles (8)(9)(10)48), and the energetic effects of mutations can have as much to do with surrounding structural rearrangements in response to hydrogen bond ablation as they do with properties of the hydrogen bonds themselves (49)(50)(51)(52). In contrast to these common mutagenic approaches, we have leveraged favorable features of KSI to interrogate the physical and energetic properties of the intact hydrogen bond network formed in the KSI active site and to study the effects of internal charge rearrangement on electrostatic fields within the active site.…”

Section: Discussionmentioning

confidence: 99%

Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site

Sigala¹,

Fafarman²,

Schwans³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Hydrogen bond networks are key elements of protein structure and function but have been challenging to study within the complex protein environment. We have carried out in-depth interrogations of the proton transfer equilibrium within a hydrogen bond network formed to bound phenols in the active site of ketosteroid isomerase. We systematically varied the proton affinity of the phenol using differing electron-withdrawing substituents and incorporated sitespecific NMR and IR probes to quantitatively map the proton and charge rearrangements within the network that accompany incremental increases in phenol proton affinity. The observed ionization changes were accurately described by a simple equilibrium proton transfer model that strongly suggests the intrinsic proton affinity of one of the Tyr residues in the network, Tyr16, does not remain constant but rather systematically increases due to weakening of the phenol-Tyr16 anion hydrogen bond with increasing phenol proton affinity. Using vibrational Stark spectroscopy, we quantified the electrostatic field changes within the surrounding active site that accompany these rearrangements within the network. We were able to model these changes accurately using continuum electrostatic calculations, suggesting a high degree of conformational restriction within the protein matrix. Our study affords direct insight into the physical and energetic properties of a hydrogen bond network within a protein interior and provides an example of a highly controlled system with minimal conformational rearrangements in which the observed physical changes can be accurately modeled by theoretical calculations.computational modeling | enzyme catalysis | protein electrostatics | protein semisynthesis | active site environment H ydrogen bond networks are ubiquitous structural features within proteins, and they play key roles linking secondary and tertiary structural elements and spanning protein-protein interfaces. Such networks are especially common within enzyme active sites, where they position protein and substrate groups for catalysis, stabilize charge rearrangements during chemical transformations, and mediate proton transfers (1). Despite the prevalence and critical structural and functional roles of hydrogen bond networks, incisive dissection of their physical properties within the idiosyncratic interior of folded proteins remains difficult.Hydrogen-bonded protons are not observed in the vast majority of protein X-ray structures due to the low X-ray scattering power of hydrogen atoms (2). Thus, the presence of hydrogen bond networks is typically inferred from the proximity and orientation of hydrogen bond donor and acceptor groups within refined protein structural models. The inherent inability of most X-ray diffraction studies to monitor proton positions imposes additional challenges for dissecting the physical features that influence the equilibrium protonation states of specific residues along a hydrogen-bonded proton transfer network. Furthermore, it remains extremely challenging t...

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“…Protein-protein interaction occurs at active site of polar or charged residues and water molecules creating a hydrogen bond networks for proton transfer pathways [Ishikita and Saito, 2013]. During protein interaction at the active site of protein domains occurs hydrogen bonding between secondary structure elements generating complex and dynamic proton network system which has crucial role in signaling [Derege et al, 1995].Dynamics of an active site depends on hydrogen bond stability [Sigala et al, 2009]. If hydrogen bond with O─O distance is les of 2.7Ah ydrogen bond is sensitive to trivial perturbation [Radisavljevic, 2003[Radisavljevic, , 2004a[Radisavljevic, ,b, 2008[Radisavljevic, , 2013a[Radisavljevic, ,b,c, 2015a[Radisavljevic, ,b, 2016Sigala et al, 2009] such as substitution of hydrogen by deuterium which changes free energy of hydrogen bond resulting in lengthening of the O─O distance [Ichikawa, 2000].…”

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confidence: 99%

AKT as Locus of Hydrogen Bond Network in Cancer

Radisavljevic

2017

J of Cellular Biochemistry

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Generation and maintenance of a cancer complexity and robustness are impossible without hydrogen element. It is essential element for the cancer signaling through the AKT locus. Hyperactivated AKT locus by a positive feedback loops from the cancer hypoxic microenvironment generates a hydrogen bond network. Such network initiates protein-protein interaction at the AKT active site and at the same time stabilizes signal propagation. A hydrogen bond network conforms an entropy/enthalpy energetic process used for the interconversion of the AKT protein in metastasis formation and maintenance. Targeting the AKT locus by the redox balance change or hydrogen balance change or proton beam radiation disrupts a hydrogen bond network leading to the disappearance of a cancer complexity and robustness causing failure of the complex energy system in solid cancers and hematological malignancy. J. Cell. Biochem. 119: 130-133, 2018. © 2017 Wiley Periodicals, Inc. KEY WORDS: HYDROGEN BOND NETWORK; AKT LOCUS; CANCER SIGNALING; CANCER ROBUSTNESS AND COMPLEXITYI nitiation of signaling begins at active site of interacting proteins by a hydrogen bonds conformation. However, propagation of signals is achieved by the hydrogen bond stabilization at the active site. Thus, signal transduction network generation and propagation relay on hydrogen bonds. Hydrogen is essential element in cancer signaling. AKT as a locus of cancer robustness and fragility [Radisavljevic, 2004a[Radisavljevic, , b, 2008[Radisavljevic, , 2013a[Radisavljevic, ,b,c, 2015a[Radisavljevic, ,b, 2016 functions trough the hydrogen bonds. Targeting hydrogen bond as a specific element in signaling could be achieved by the hydrogen balance change which will cause complete failure of cancer robustness and complexity. Network of the complex signaling pathways for cancer cell proliferation through the Rb/AKT/NO pathway [Radisavljevic, 2004b] and the PI3 K/AKT/mTOR/ RAN pathway [Radisavljevic and Gonzalez-Flecha, 2004], cell migration through the VEGF/AKT/ICAM1 pathway [Radisavljevic et al., 2000] are achieved by the hydrogen bonds at active sites [Ishikita and Saito, 2013;Liu et al., 2015] of the AKT locus [Radisavljevic et al., 2000;Radisavljevic, 2004a Radisavljevic, ,b, 2008Radisavljevic, , 2013a Radisavljevic, ,b,c, 2015a Radisavljevic, ,b, 2016Radisavljevic and Gonzalez-Flecha, 2004]. AKT LOCUS OF HYDROGEN BOND NETWORKS IN CANCER ROBUSTNESS AND FRAGILITYHydrogen molecule is essential for a living cell function. Such function is a cell signaling which involves protein interactions. Hydrogen bonds are essential in the protein-protein interaction making a hydrogen bond networks and cell energetics crucial in the protein conformation change [Ishikita and Saito, 2013]. Initiation of signaling, stabilization, and propagation of signals in a cancer hypoxic microenviroment is crucial for the interacting proteins [Radisavljevic, 2004a[Radisavljevic, ,b, 2008[Radisavljevic, , 2013a[Radisavljevic, ,b,c, 2015a[Radisavljevic, ,b, 2016. Protein-protein interaction occ...

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Hydrogen bond dynamics in the active site of photoactive yellow protein

Cited by 78 publications

References 48 publications

Proton transfer reactions and hydrogen-bond networks in protein environments

Proton transfer reactions and hydrogen-bond networks in protein environments

Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site

AKT as Locus of Hydrogen Bond Network in Cancer

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