Conformations of JNK3α splice variants analyzed by hydrogen/deuterium exchange mass spectrometry

Park, Ji Young,Yun, Youngjoo,Chung, Ka Young Elsevier 2017 Journal of structural biology Vol.197 No.3

<P>c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family that regulate apoptosis, inflammation, cytokine production, and metabolism. MAPKs undergo various splicing within their kinase domains. Unlike other MAPKs, JNKs have alternative splicing at the C-terminus, resulting in long and short variants. Functional or conformational effects due to the elongated C-terminal tail in the long splice variants have not been investigated nor has the conformation of the C-terminal tail been analyzed. Here, we analyzed the conformation of the elongated C-terminal tail and investigated conformational differences between long and short splice variants of JNKs using JNK3 alpha 2 and JNK3 alpha 1 as models. We adopted hydrogen/deuterium exchange mass spectrometry (HDX-MS) to analyze the conformation. HDX-MS revealed that the C-terminal tail is mostly intrinsically disordered, and that the conformation of the kinase domain of JNK3 alpha is more dynamic than that of JNK3 alpha 1. The different conformation dynamics between long and short splice variants of JNK3 alpha might affect the cellular functions of JNIG. (C) 2016 Elsevier Inc. All rights reserved.</P>

Single-Chain Conformational Characteristics of Comb-Like Polyelectrolytes: Molecular Dynamics Simulation Study

Soheila Emamyari,Hossein Fazli 한국고분자학회 2019 Macromolecular Research Vol.27 No.1

The single-chain conformation of a model comb polyelectrolyte, in which the electric charges are located on the last monomer of side chains, has been studied using molecular dynamics simulations. The model chain has a hydrophobic backbone and hydrophilic side chains. The influence of parameters such as the length of backbone and side chains, the grafting density of side chains, flexibility of the chain and different strengths of backbone hydrophobicity have been investigated. At high grafting density of side chains, a transition from turn to pearl-necklace and finally to globular conformation is observed by increasing the hydrophobicity. Radius of gyration (R g) of the backbone depends linearly on the number of backbone monomers at low values of the backbone hydrophobicity, but at high values of the backbone hydrophobicity, because of the appearance of turn-like segments between successive globular sections in the pearl-necklace structure, the scaling exponent of R g versus N is larger. Also, the chain flexibility affects the backbone conformation significantly. The increase of the persistence length leads to the appearance of the folded and then the extended conformations. In addition to the statistical properties of the chains, the investigation of the relaxation of the chains conformation shows that, the backbone takes almost its final conformation in the early time steps of the simulation for all conditions. It means that the relaxation time of the chain is relatively short (fast relaxation).

Aldehydic Nature and Conformation of 3,6-Anhydro-L-galactose Monomer

이선복,이신엽,임현승 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.5

We investigated the aldehydic nature and conformation of 3,6-anhydro-L-galactose (L-AnG) by using enzymes that bind L-AnG in a reactive conformation. We found that L-AnG, but not L-galactose, can be oxidized by E. coli L-lactaldehyde dehydrogenase (Ec_LADH); this observation suggests that L-AnG is an aldehyde belonging to the α-hydroxyaldehyde family. Because the native enzyme that catalyzes oxidation of L-AnG to its carboxylate is LAnG dehydrogenase (L-AnGDH), we compared the crystal structure and amino-acid sequences of Ec_LADH with those of L-AnGDHs. This analysis revealed that the two oxygen atoms in the α-hydroxyaldehyde moiety of L-AnG are essential for the reactions of Ec_LADH and LAnGDHs. A chemical database search indicated that two configurations of L-AnG are possible: a trans arrangement in which C-2 and C-5 hydroxyl groups are on the opposite side and a cis arrangement in which these groups are on the same side. Manual docking of the two forms of L-AnG into the active site of Pseudoalteromonas atlantica LAnGDH (Pa_L-AnGDH) revealed that only the trans LAnG configuration can be fitted into the active site of Pa_L-AnGDH. The identification of trans L-AnG suggests the existence of three L-AnG conformations: bicyclic pyranose, opened pyranose, and open-chain aldehyde. The conformation of L-AnG monomer (open-chain aldehyde) differs from that in agarose (bicyclic pyranose) or agarobiose (opened pyranose) because a five-membered anhydro ring is free to move and can find its most stable conformation. This study validates the assumption of trans-type open-chain aldehyde conformation of L-AnG that was applied in our previous studies.

Factor Analysis of Biometric Traits of Kankrej Cows to Explain Body Conformation

Pundir, R.K.,Singh, P.K.,Singh, K.P.,Dangi, P.S. Asian Australasian Association of Animal Productio 2011 Animal Bioscience Vol.24 No.4

Eighteen different biometric traits in 407 Kankrej cows from their breeding zone, i.e. Palanpur district of Gujarat, India, were recorded and analyzed by factor analysis to explain body conformation. The averages of body length, height at withers, height at shoulder, height at knee, heart girth, paunch girth, face length, face width, horn length, horn diameter, distance between horns, ear length, ear width, neck length, neck diameter, tail length with switch, tail length without switch and distance between hip bones were $123.44{\pm}0.37$, $124.49{\pm}0.28$, $94.68{\pm}0.30$, $38.2{\pm}0.14$, $162.56{\pm}0.56$, $178.95{\pm}0.70$, $44.09{\pm}0.10$, $15.91{\pm}0.05$, $42.47{\pm}0.53$, $26.07{\pm}0.19$, $13.34{\pm}0.08$, $31.24{\pm}0.12$, $16.10{\pm}0.05$, $50.63{\pm}0.18$, $73.21{\pm}0.32$, $111.62{\pm}0.53$, $89.34{\pm}0.34$ and $17.28{\pm}0.10\;cm$, respectively. The correlation coefficients between different traits ranged from -0.806 (horn diameter and distance between horns) to 0.815 (heart girth and paunch girth). Most of the correlations were positive and significant. Factor analysis with promax rotation with power 3 revealed three factors which explained about 66.02% of the total variation. Factor 1 described the cow body and explained 38.89% of total variation. The second factor described the front view/face of the cow and explained 19.68% of total variation. The third factor described the back of the cow and explained 7.44% of total variation. It was necessary to include some more variables for factor 3 to obtain a reliable estimate of the back view of the cow. The lower communities shown for distance between horns, horn diameter, ear width and neck diameter indicated that these traits did not contribute effectively to explaining body conformation and can be dropped from recording, whereas all other traits are important and needed to explain body conformation in Kankrej cows. The result suggests that principal component analysis (PCA) could be used in breeding programs with a drastic reduction in the number of biometric traits to be recorded to explain body conformation.

트롬복산 A2와 트롬복산 A2 수용체 길항제의 활성형태

이종달(Jong Dal Rhee),도성탁(Seong Tak Doh) 대한약학회 1997 약학회지 Vol.41 No.6

Conformational analyses on thromboxane A2 (TxA2) and thromboxane A2 receptor antagonists (TxRA) were carried out by molecular mechanics method. Based on the assumption that active conformer is the nonintrahydrogen bonding and more stable former of TxA2 and TxRA, the molecular structural requirements for potent TxA2 receptor antagonists are like below: 1) The distance is 5.0-5.6 A.U. between C atom of carboxyl group and S atom of sulfonyl group or C atom which is bonded to hydroxyl group in the active conformers. 2) The putative active conformers of TxA2 and TxRAs are hairpin-like forms.

Sulfonylurea 유도체들의 구조분석 : Acetohexamide와 Tolazamide

정우태,강기롱,이성희 대한약학회 1995 약학회지 Vol.39 No.3

Conformational free energy calculations using an empirical potential function and a hydration shell model(program CONBIO) were carried out on hypoglycemic agent acetohexamide and tolazamide in the unhydrated and hydrated states. The initial geometry of sulfonylureas was obtained from X-ray crystallographieal data and homologous molecular fragments. In both states, the feasible conformations were obtained from the calculations of conformational energy, conformational entropy, and hydration free energy by varying all the torsion angles of the molecules. From the calculation results, it is known that the conformations] entropy is the major contribution to stabflize the low-free-energy conformations of two sulfonylureas in both states. But, in hydrated state, the hydration does not directly affect each conformations. The intramolecular hydrogen bonding of sulfonylurea hydrogen and 7-membered nitrogen appeared to the conformations of tolazamide in both states. It is thought that the hydrogen bonding decrease steric hindrance on the receptor binding direction. The substitution of alicyclic or N-heterocyclic ring than that of carbons chain of urea moiety may be properly interaction between sulfonylureas and the putative pancreatic receptor.

γ-(Trityloxymethy1)-γ-Butyrolactone 유도체의 배좌연구

김희두 숙명여자대학교 약학연구소 1995 약학논문집-숙명여자대학교 Vol.11 No.-

To elucidate the controlling factor to take special gauche(+) conformation in γ-(trityloxymethyl)-γ-butyrolactone, β-(trityloxymethyl)-γ-butyrolactone, 2-(benzyloxymethyl)tetrahydrofuran-4-one, and 2-(trityloxymethyl) tetrahydrofuran were analyzed their conformations by ^1H-NMR analysis. Attractive gauche effect and n↔π^* interaction seems to be operative as the major intramolecular interactions to stabilize the conformation.

트롬복산 A₂와 트롬복산 A₂ 수용체 길항제의 활성형태

이종달,도성탁 영남대학교 약품개발연구소 1998 영남대학교 약품개발연구소 연구업적집 Vol.8 No.-

Conformational analyses on thromboxane A₂ (TxA₂) and thromboxane A₂ receptor antagonists (TxRA) were carried out by molecular mechanics method. Based on the assumption that active conformer is the nonintrahydrogen bonding and more stable former of TxA₂ and TxRA the molecular structural requirements for potent TxA₂ receptor antagonists are like below: 1) The distance is 5.0~5.6Å between C atom of carboxyl group and S atom of sulfonyl group or C atom which is bonded to hydroxyl group in the active conformers. 2) The putative active conformers of TxA₂ and TxRAs are hairpin-like forms.

제주마 체형 기능적 특성과 경주능력간의 분석

오운용,김병우,조현우,신택순,조성근,조병욱 경상대학교 농업생명과학연구원 2014 농업생명과학연구 Vol.48 No.1

The conformation of a horse is closely related to its function as a performing individual. Also, from the evolutionarily of point view, it should be corrected well too for the type of work required of the horse. Jeju horses are characterized as small in height and resilient. They used to be a means of power in plowing and transportation in ancient times in Korea. Most horses are being raised today for horse racing. The aim of this study was to investigate the relationships between conformation and racing performance that would be used for selection of superior breeding stocks on racing speed of Jeju horses. Eighteen skeletal segments were monitored in 92 Jeju horses and 81 Thoroughbreds. Withers height was measured directly. Other 17 lengths were calculated from conformational photographs in which withers height was measured. Racing records were collected from Jeju Race Park from February 2002 to November 2004. For statistical analysis, PRINCOMP and GLM of SAS were used. The first to sixth principal components(PCs), sex and age groups were included as variables in GLM. The first to six PCs together accounted for 67.1% of the total variation. Racing performance measured by speed was significantly correlated to PC2(P<.001). This result indicates that horses that are long in neck bottom line and scapula and are short in radius and gaskin simultaneously are able to run faster. These results can be support the notion that selection of Jeju horses for racing speed that should be guided by general balance of conformation. Further study may be needed with more data to increase accuracy of investigation. 말의 형태는 기능적으로 개별적으로 실행 할 수 있는 능력과 연관이 깊다. 또한, 진화론적 관점으로 말의 형태는 말이 요구되는 일의 유형에 따라 적합하게 변화되어야 한다. 제주마의 경우에는 체형이 작고, 근육의 탄력이 적은 특징을 가지고 있다. 위 특징은 제주마가 국내의 경우 과거에 짐의 운반과 경운에 유용하게 이용되어졌음을 의미한다. 오늘날 말들은 거의 경주마로써 육성되고 있다. 본 연구의 목적은 말의 형태와 경주능력간의 관계에 대해 규명하고, 이 관계는 우수한 육종가의 선발에 사용될 수 있음을 기대한다. 본 연구는 경주성적이 있는 제주마 92 두와 더러브렛종 81두의 골격근 18 개 부분과 형태와 체고를 직접적으로 측정하여 확인했다. 또한, 실측 체고치와 측면 이미지 자료로부터 17 부위의 길이를 쟀다. 연구에 사용된 경주기록은 2002 년 2 월부터 2004 년 11 월까지 제주 경주 공원으로부터 수집하여 사용했고, 통계분석은 SAS프로그램을 사용하여 PRINCOMP와 GLM을 분석 실시하였다. 성, 나이로 그룹을 설정하여 GLM의 다양성에 따라 분류하여 주성분분석을 실시한 결과, 제 1~6 주성분 PCs 간의 전체 변이는 67.1%로 계산되었고, 경주수행정도는 속도 어깨와 목길이가 길고 전박장과 엉덩이 길이가 짧은 특징을 나타낸 제 2 주성분(PC2)에 유사하게 상관되게 측정되었다(P<.001). 위 결과에 따르면 말의 여러 가지 형태적 특징 중, 말의 목 하단길이와 견갑골이 길며, 전완골과 정강이가 짧은 형태를 가질 경우 빠르게 달릴 수 있다는 것으로 나타났다. 이러한 연구 결과는 제주마의 경주 속도가 일반적인 형태적 균형에 의해 좌우될 수 있다는 개념을 시사한다. 또한, 본 연구는 더 많은 데이터가 있었다면, 조사의 정확성이 향상될 수 있음을 시사한다.

Phosphorylation alters backbone conformational preferences of serine and threonine peptides

Kim, Su‐,Yeon,Jung, Youngae,Hwang, Geum‐,Sook,Han, Hogyu,Cho, Minhaeng Wiley Subscription Services, Inc., A Wiley Company 2011 Proteins Vol.79 No.11

<P><B>Abstract</B></P><P>Despite the notion that a control of protein function by phosphorylation works mainly by inducing its conformational changes, the phosphorylation effects on even small peptide conformation have not been fully understood yet. To study its possible effects on serine and threonine peptide conformations, we recently carried out pH‐ and temperature‐dependent circular dichroism (CD) as well as <SUP>1</SUP>H NMR studies of the phosphorylated serine and threonine peptides and compared them with their unphosphorylated analogs. In the present article, by performing the self‐consistent singular value decomposition analysis of the temperature‐dependent CD spectra and by analyzing the <SUP>3</SUP>J(H<SUB>N</SUB>,H<SUB>α</SUB>) coupling constants extracted from the NMR spectra, the populations of the polyproline II (PPII) and β‐strand conformers of the phosphorylated Ser and Thr peptides are determined. As temperature is increased, the β‐strand populations of both phosphorylated serine and threonine peptides increase. However, the dependences of PPII/β‐strand population ratio on pH are different for these two cases. The phosphorylation of the serine peptide enhances the PPII propensity, whereas that of the threonine peptide has the opposite effect. This suggests that the serine and threonine phosphorylations can alter the backbone conformational propensity via direct but selective intramolecular hydrogen‐bonding interactions with the peptide NH groups. This clearly indicates that the phosphoryl group actively participates in modulating the peptide backbone conformations. Proteins 2011; © 2011 Wiley‐Liss, Inc.</P>