Inhibition of tyrosinase by fumaric acid: Integration of inhibition kinetics with computational docking simulations

Gou, L.,Lee, J.,Yang, J.M.,Park, Y.D.,Zhou, H.M.,Zhan, Y.,Lu, Z.R. Elsevier 2017 International Journal of Biological Macromolecules Vol.105 No.3

Fumaric acid (FA), which is naturally found in organisms, is a well known intermediate of the citric acid cycle. We evaluated the effects of FA on tyrosinase activity and structure via enzyme kinetics and computational simulations. FA was found to be a reversible inhibitor of tyrosinase and its induced mechanism was the parabolic non-competitive inhibition type with IC<SUB>50</SUB>=13.7+/-0.25mM and K<SUB>islope</SUB>=12.64+/-0.75mM. We newly established the equation for the dissociation constant (K<SUB>islope</SUB>) for the parabolic inhibition type in this study. Kinetic measurements and spectrofluorimetry studies showed that FA induced regional changes in the active site of tyrosinase. One possible binding site for FA was identified under the condition without L-DOPA. The computational docking simulations further revealed that FA can interact with HIS263 and HIS85 at the active site. Furthermore, four important hydrogen bonds were found to be involved with the docking of FA on tyrosinase. Our study provides insight into the mechanism by which dicarboxylic acids such as FA inhibit tyrosinase. By inhibiting tyrosinase and its central role in pigment production, FA is a potential natural antipigmentation agent.

Effects of L-malic acid on alpha-glucosidase: inhibition kinetics and computational molecular dynamics simulations.

Gou, Lin,Zhan, Yi,Lee, Jinhyuk,Li, Xuan,Lü,, Zhi-Rong,Zhou, Hai-Meng,Lu, Hang,Wang, Xi-Yao,Park, Yong-Doo,Yang, Jun-Mo Humana Press 2015 Applied biochemistry and biotechnology Vol.175 No.4

<P>The inhibitory effect of L-malic acid (MA) on alpha-glucosidase (EC 3.2.1.20) was investigated by combination study between inhibition kinetics and computational simulations. The results from the serial kinetics demonstrated that MA could directly inactivate the enzyme activity in a dose-dependent manner and a typical non-competitive type, as well as in a fast inactivate process without detectable time course. The tertiary conformation study with an application of spectrofluorimetry showed that MA modulated the tertiary structural conformation of alpha-glucosidase both on the overall and on regional active site pocket, which monitored by red-shift intrinsic fluorescence peak with decreases intensities, and the significant intensity increasing of 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence, respectively. To have more insight, we also adapted the computational molecular dynamics (MD) simulations. The results showed that MA was located in the entrance of active pocket for the catalytic reaction and blocked the passage of substrate. It confirmed that MA inhibits as a non-competitive type, not direct docking to the glucose binding site. Our study provides important molecular mechanisms to figure out alpha-glucosidase inhibition that might associate to development of type 2 diabetes mellitus drug.</P>

Epitaxial Multiferroic BiFeO3 Thin Films: Progress and Future Directions

Chu, Y. H.,Martin, L. W.,Zhan, Q.,Yang, P. L.,Cruz, M. P.,Lee, K.,Barry, M.,Yang, S. Y.,Ramesh, R. Taylor Francis 2007 Ferroelectrics Vol.354 No.1

<P> We write this article in honor of Professor Vitaly L. Ginzburg, truly the father of the field of ferroelectricity. This article serves as a review of the current state of research pertaining to multiferroic BiFeO3 thin films. In this review we will delve into details of the growth of BiFeO3 thin films and the use of piezoforce microscopy and x-ray reciprocal space mapping to characterize the crystal structure and domain structure of BiFeO3. We will also discuss the use of vicinal and asymmetric substrates to simplify the domain structure in BiFeO3. By simplifying the domain structure we can, in turn, control the ferroelectric switching mechanisms in BiFeO3. Finally we describe the basic ferroelectric properties of BFO films and discuss the critical issues needed to be solved in BiFeO3 films including leakage, complex domain structure, coercivity, and reliability. Such results are promising for continued exploration for detailed multiferroic-coupling studies in the magnetoelectric BiFeO3 system and BiFeO3, in turn, provides a model platform with which to realize the exciting possibility of electrically control magnetism.</P>

Effect of night light regimen on growth performance, antioxidant status and health of broiler chickens from 1 to 21 days of age

R.X. Zhao,C.H. Cai,P. Wang,L. Zheng,J.S. Wang,K.X. Li,W. Liu,X.Y. Guo,X. A. Zhan,K.Y. Wang 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.6

Objective: The study was conducted to evaluate the effects of night light regimen on growth performance, antioxidant status and health of Lingnan Yellow broiler chickens from 1 to 21 days of age. Methods: A completely randomized factorial design involved 2 photoperiods (constant lighting [CL], 24 L:0 D and intermittent lighting [INL], 17 L:3 D:1 L:3 D)×2 light intensities (10 lx and 30 lx). A total of one thousand six hundred and eighty 1-d-old Lingnan Yellow broiler chicks were randomly divided into 4 treatments with 6 replicates (70 birds per replicate). The experiment lasted for 21 d. Results: Photoperiods and light intensities had no effect on average daily gain, feed conversion ratio, and mortality of the broiler chickens (p>0.05). The INL had a significant effect on average daily feed intake (p<0.05) of broiler chickens compared with CL. Photoperiod and light intensity had an interactive effect on melatonin (MT) concentration (p<0.05). At CL, reducing light intensity increased MT concentration; INL birds had higher MT but MT concentration was not affected by light intensity. There was an interactive effect on glutathione peroxidase (GPx) and catalase (CAT) in serum and total antioxidant capability (T-AOC) in liver between photoperiod and light intensity. With the decrease of light intensity, the activities of GPx and CAT in serum and T-AOC in liver increased in CL group (p<0.05). Broiler chickens reared under INL had better antioxidant status and 10 lx treatments had higher activities of CAT in serum than 30 lx (p<0.05). Different photoperiods and light intensities had no effect on malondialdehyde. There was an interaction between photoperiod and light intensity on serum creatine kinase (CK) concentration (p<0.05). At CL, the elevated light intensity resulted in an increase in CK content; INL birds had lower CK concentration especially in low light intensity group. Besides, INL and low light intensity significantly reduced the concentration of serum corticosterone and heat shock protein 70 (p<0.05). Serum immunoglobulin M contents were increased in broiler chickens reared under the INL compared with CL group (p<0.05). Conclusion: Results above suggest that the night light regimen of INL and 10 lx could be beneficial to the broiler chickens from 1 to 21 days of age due to the better health status and electricity savings.

<Retraction> INVESTIGATION OF HIGH-COERCIVITY FePt-C NANOGRANULAR FILMS FOR PERPENDICULAR MAGNETIC RECORDING (PMR) MEDIA

JIEGANG PENG,S. XUE,Z. YAN,X. WU,L. ZHAN 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2011 NANO Vol.6 No.6

In this work, we studied FePt-C nanogranular films were fabricated for ultrahigh density perpendicular recording media towards 1 Tbits/in^2. For the optimized growth conditions, we achieved a Fe_(52)Pt_(48)-C50% granular film with uniform grain size of 6.4 ± 1.5 nm, shown in the TEM image. It also has an excellent MH loop shape with a perpendicular coercivity of 20 kOe, and squareness of 1.We studied the thermal stability of the optimized film and obtained the energy barrier Eb of 340 k_BT at room temperature, meaning that excellent thermal stability as magnetic recording media.

Plastification procedure of laterally-loaded steel bars under a rising temperature

Zhan-fei Huang,Kang-hai Tan,George L. England 국제구조공학회 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.35 No.6

This paper investigates the structural responses of axially restrained steel beams under fire conditions by a nonlinear finite element method. The axial restraint is represented by a linear elastic spring. Different parameters which include beam slenderness ratio, external load level and axial restraint ratio are investigated. The process of forming a mid-span plastic hinge at the mid-span under a rising temperature is studied. In line with forming a fully plastic hinge at mid-span, the response of a restrained beam under rising temperature can be divided into three stages, viz. no plastic hinge, hinge forming and rotating, and catenary action stage. During catenary action stage, the axial restraint pulls the heated beam and prevents it from failing. This study introduces definitions of beam limiting temperature Tlim, catenary temperature Tctn and warning time twn. Influences of slenderness ratio, load level and axial restraint ratio on Tlim, Tctn and twn are examined.

Cyclo[6]pyridine[6]pyrrole: A Dynamic, Twisted Macrocycle with No Meso Bridges

Zhang, Zhan,Cha, Won-Young,Williams, Neil J.,Rush, Elise L.,Ishida, Masatoshi,Lynch, Vincent M.,Kim, Dongho,Sessler, Jonathan L. American Chemical Society 2014 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.136 No.21

<P>A large porphyrin analogue, cyclo[6]pyridine[6]pyrrole, containing no meso bridging atoms, has been synthesized through Suzuki coupling. In its neutral form, this macrocycle exists as a mixture of two figure-eight conformers that undergo fast exchange in less polar solvents. Upon protonation, the dynamic twist can be transformed into species that adopt a ruffled planar structure or a figure-eight shape depending on the extent of protonation and counteranions. Conversion to a bisboron difluoride complex via deprotonation with NaH and treatment with BF<SUB>3</SUB> acts to lock the macrocycle into a figure-eight conformation. The various forms of cyclo[6]pyridine[6]pyrrole are characterized by distinct NMR, X-ray crystallographic, and spectroscopic features.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-21/ja503451m/production/images/medium/ja-2014-03451m_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja503451m'>ACS Electronic Supporting Info</A></P>

Plastification procedure of laterally-loaded steel bars under a rising temperature

Huang, Zhan-Fei,Tan, Kang-Hai,England, George L. Techno-Press 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.35 No.6

This paper investigates the structural responses of axially restrained steel beams under fire conditions by a nonlinear finite element method. The axial restraint is represented by a linear elastic spring. Different parameters which include beam slenderness ratio, external load level and axial restraint ratio are investigated. The process of forming a mid-span plastic hinge at the mid-span under a rising temperature is studied. In line with forming a fully plastic hinge at mid-span, the response of a restrained beam under rising temperature can be divided into three stages, viz. no plastic hinge, hinge forming and rotating, and catenary action stage. During catenary action stage, the axial restraint pulls the heated beam and prevents it from failing. This study introduces definitions of beam limiting temperature $T_{lim}$, catenary temperature $T_{ctn}$ and warning time $t_{wn}$. Influences of slenderness ratio, load level and axial restraint ratio on $T_{lim}$, $T_{ctn}$ and $t_{wn}$ are examined.

The effect of alpha-ketoglutaric acid on tyrosinase activity and conformation: Kinetics and molecular dynamics simulation study

Gou, L.,Lee, J.,Yang, J.M.,Park, Y.D.,Zhou, H.M.,Zhan, Y.,Lu, Z.R. Elsevier 2017 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.105 No.3

Alpha-ketoglutaric acid (AKG) is naturally found in organisms and is a well-known intermediate in the production of ATP or GTP in the Krebs cycle. We elucidated the effects of AKG on tyrosinase activity and conformation via methods of inhibition kinetics integrated with molecular dynamics (MD) simulations. AKG was found to be a reversible inhibitor of tyrosinase (IC<SUB>50</SUB>=15+/-0.5mM) and induced parabolic slope mixed-type inhibition. Based on our newly established equation, the dissociation constant (K<SUB>islope</SUB>) was determined to be 7.93+/-0.31mM. The spectrofluorimetry studies showed that AKG mainly induced regional changes in the active site of tyrosinase, which reflects the flexibility of the active site. The computational docking and molecular dynamics (MD) simulations further demonstrated that AKG could interact with several residues near the substrate-binding site located in the tyrosinase active site pocket. Our study provides insight into the mechanism by which energy-producing intermediates such as AKG inhibit tyrosinase through its ketone groups. Also, AKG could be a potential natural antipigmentation agent due to its non-toxic property.

Cyclo[<i>m</i>]pyridine[<i>n</i>]pyrroles: Hybrid Macrocycles That DisplayExpanded π-Conjugationupon Protonation

Zhang, Zhan,Lim, Jong Min,Ishida, Masatoshi,Roznyatovskiy, VladimirV.,Lynch, Vincent M.,Gong, Han-Yuan,Yang, Xiaoping,Kim, Dongho,Sessler, Jonathan L. American Chemical Society 2012 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.134 No.9

<P>Novel hybrid cyclo[<I>m</I>]pyridine[<I>n</I>]pyrroles have been synthesized using Suzuki coupling.Their NMRand optical spectroscopic features and solid state structural parametersprovide support for the proposal that these species are best describedas locally aromatic compounds devoid of long-range intersubunit conjugation.However, an extension of the π-conjugation in the macrocyclescan be realized through protonation, as inferred from optical spectroscopicand X-ray diffraction-based structural studies.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2012/jacsat.2012.134.issue-9/ja211985k/production/images/medium/ja-2011-11985k_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja211985k'>ACS Electronic Supporting Info</A></P>