scholarly journals Interactions of tervalent lanthanide ions with bacterial collagenase (clostridiopeptidase A)

1981 ◽  
Vol 195 (3) ◽  
pp. 677-684 ◽  
Author(s):  
Christopher H. Evans
Keyword(s):  
Ionic Radius ◽  
Substrate Inhibition ◽  
Volume Ratio ◽  
Binding Pocket ◽  
Lanthanide Ions ◽  
Ionic Radii ◽  
Apparent Dissociation Constant ◽  
Substrate Complex ◽  
Bacterial Collagenase ◽  
Hydrolysis Of

Tervalent cations of the lanthanide (rare-earth) elements reversibly inhibit bacterial collagenase (clostridiopeptidase A; EC 3.4.24.3). Sm3+, whose ionic radius is closest to that of Ca2+, is the most effective inhibitor, completely suppressing clostridiopeptidase activity at a concentration of 100μm in the presence of 5mm-Ca2+. Er3+ and Lu3+, which both have ionic radii smaller than either Ca2+ or Sm3+, inhibit less efficiently, and La3+, which is slightly larger than Ca2+ or Sm3+, inhibits only weakly. These findings indicate a closely fitting, stereospecific, Ca2+-binding pocket in clostridiopeptidase, which excludes ions that are only slightly larger than Ca2+ [ionic radius 0.099nm (0.99 Ȧ)]. By contrast, trypsin, an enzyme whose activity does not depend on Ca2+, requires lanthanide concentrations 50–100-fold greater for inhibition. Furthermore, the relative efficiency of inhibition of trypsin by lanthanides increases as the lanthanide ions become smaller and the charge/volume ratio increases. At a concentration of 50μm, Sm3+ lowers the apparent Km for the hydrolysis of Pz-peptide by clostridiopeptidase from 5.4mm to 0.37mm and the apparent Vmax. from 0.29 Wünsch–Heidrich unit to 0.018 unit. Thus Sm3+ enhances the affinity of this enzyme for its substrate; inhibition of hydrolysis of Pz-peptide may result from the excessive stability of the enzyme–Sm3+–substrate complex. Inhibition by Sm3+ is competitive with regard to Ca2+. The apparent dissociation constant, Kd, of Ca2+ is 0.27mm, where the Ki for Sm3+ is 12μm. Clostridiopeptidase is more thermolabile in the absence of Ca2+. With Sm3+, thermoinactivation of the enzyme at 53°C or 60°C is initially accelerated, but then becomes retarded as heating continues. Lanthanide ions bind to gelatin and collagen. In so doing, they appear to protect these substrates from lysis by clostridiopeptidase through mechanisms additional to supplanting Ca2+ at its binding site on the enzyme. Collagen and gelatin sequester sufficient lanthanide ions to gain partial protection from clostridiopeptidase in the absence of an extraneous source of these inhibitors.

scholarly journals The origins of binding specificity of a lanthanide ion binding peptide

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takaaki Hatanaka ◽  
Nobuaki Kikkawa ◽  
Akimasa Matsugami ◽  
Yoichi Hosokawa ◽  
Fumiaki Hayashi ◽  
...  
Keyword(s):  
Water Molecule ◽  
Ionic Radius ◽  
Binding Specificity ◽  
Lanthanide Ions ◽  
Ion Binding ◽  
Deep Insight ◽  
Ionic Radii ◽  
Linear Peptide ◽  
High Affinity ◽  
Insight Into

Abstract Lanthanide ions (Ln3+) show similar physicochemical properties in aqueous solutions, wherein they exist as + 3 cations and exhibit ionic radii differences of less than 0.26 Å. A flexible linear peptide lanthanide binding tag (LBT), which recognizes a series of 15 Ln3+, shows an interesting characteristic in binding specificity, i.e., binding affinity biphasically changes with an increase in the atomic number, and shows a greater than 60-fold affinity difference between the highest and lowest values. Herein, by combining experimental and computational investigations, we gain deep insight into the reaction mechanism underlying the specificity of LBT3, an LBT mutant, toward Ln3+. Our results clearly show that LBT3-Ln3+ binding can be divided into three, and the large affinity difference is based on the ability of Ln3+ in a complex to be directly coordinated with a water molecule. When the LBT3 recognizes a Ln3+ with a larger ionic radius (La3+ to  Sm3+), a water molecule can interact with Ln3+ directly. This extra water molecule infiltrates the complex and induces dissociation of the Asn5 sidechain (one of the coordinates) from Ln3+, resulting in a destabilizing complex and low affinity. Conversely, with recognition of smaller Ln3+ (Sm3+ to Yb3+), the LBT3 completely surrounds the ions and constructs a stable high affinity complex. Moreover, when the LBT3 recognizes the smallest Ln3+, namely Lu3+, although it completely surrounds Lu3+, an entropically unfavorable phenomenon specifically occurs, resulting in lower affinity than that of Yb3+. Our findings will be useful for the design of molecules that enable the distinction of sub-angstrom size differences.

Study ofAandBsites order in lanthanide-doped lead titanate ferroelectric system

2016 ◽  
Vol 31 (1) ◽  
pp. 23-30
Author(s):  
A. Pentón-Madrigal ◽  
Y. Mendez-González ◽  
A. Peláiz-Barranco ◽  
F. Calderón-Piñar ◽  
L. A. S. de Oliveira ◽  
...  
Keyword(s):  
Lead Titanate ◽  
Perovskite Structure ◽  
Ionic Radius ◽  
Phonon Mode ◽  
Lanthanide Ions ◽  
X Ray Diffraction ◽  
Ionic Radii ◽  
Optical Phonon Mode ◽  
Rietveld Refinements ◽  
X Ray

Pb0.88Ln0.08TiO3ferroelectric system, whereLn= La, Sm, Eu, and Dy, has been characterized using Scanning Electron Microscopy, Raman spectroscopy, and X-ray diffraction experiments. Softening of the lowest transverse optical phonon modeE(1TO) was evaluated as a function of the rare earths’ ionic radius suggesting partial occupation of lanthanide ions at theAandBsites of the perovskite structure. Using Rietveld refinements, it has been established a higher incorporation of Ln3+ions into theAsites of the perovskite structure than that of theBsites for the studied ceramics. The occupation atBsites increases slightly with the decreases of the ionic radii of the lanthanides.

Influence of doping on crystal growth, structure and optical properties of nanocrystalline CaTiO3: a case study using small-angle neutron scattering

2015 ◽  
Vol 48 (3) ◽  
pp. 836-843 ◽  
Author(s):  
Oindrila Mondal ◽  
Manisha Pal ◽  
Ripandeep Singh ◽  
Debasis Sen ◽  
Subhasish Mazumder ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Optical Properties ◽  
Crystal Growth ◽  
Small Angle Neutron Scattering ◽  
Ionic Radius ◽  
Ionic Radii ◽  
Growth Structure ◽  
Transmission Electron ◽  
The Difference

The effect of dopant size (ionic radius) on the crystal growth, structure and optical properties of nanocrystalline calcium titanate, CaTiO3(CTO), have been studied using small-angle neutron scattering. X-ray diffraction, along with high-resolution transmission electron microscopy, confirms the growth of pure nanocrystalline CTO. Rietveld analysis reveals that the difference of ionic radii between dopant and host ions induces strain within the lattice, which significantly affects the lattice parameters. The induced strain, due to the difference of ionic radii, causes the shrinkage of the optical band gap, which is manifested by the redshift of the absorbance band. Mesoscopic structural analysis using scattering techniques demonstrates that the ionic radius of the dopant influences the agglomeration behaviour and particle size. A high-resolution transmission electron microscopy study reconfirms the formation of pure highly crystalline CTO nanoparticles.

Effect of Modifiers on the Hydrolysis of Basic and Neutral Peptides by Carboxypeptidase B

1975 ◽  
Vol 53 (7) ◽  
pp. 747-757 ◽  
Author(s):  
Graham J. Moore ◽  
N. Leo Benoiton
Keyword(s):  
Active Site ◽  
Active Sites ◽  
Kinetic Behavior ◽  
Carboxypeptidase A ◽  
Phenyllactic Acid ◽  
Carboxypeptidase B ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
Basic Peptides ◽  
Hydrolysis Of

The initial rates of hydrolysis of Bz-Gly-Lys and Bz-Gly-Phe by carboxypeptidase B (CPB) are increased in the presence of the modifiers β-phenylpropionic acid, cyclohexanol, Bz-Gly, and Bz-Gly-Gly. The hydrolysis of the tripeptide Bz-Gly-Gly-Phe is also activated by Bz-Gly and Bz-Gly-Gly, but none of these modifiers activate the hydrolysis of Bz-Gly-Gly-Lys, Z-Leu-Ala-Phe, or Bz-Gly-phenyllactic acid by CPB. All modifiers except cyclohexanol display inhibitory modes of binding when present in high concentration.Examination of Lineweaver–Burk plots in the presence of fixed concentrations of Bz-Gly has shown that activation of the hydrolysis of neutral and basic peptides by CPB, as reflected in the values of the extrapolated parameters, Km(app) and keat, occurs by different mechanisms. For Bz-Gly-Gly-Phe, activation occurs because the enzyme–modifier complex has a higher affinity than the free enzyme for the substrate, whereas activation of the hydrolysis of Bz-Gly-Lys derives from an increase in the rate of breakdown of the enzyme–substrate complex to give products.Cyclohexanol differs from Bz-Gly and Bz-Gly-Gly in that it displays no inhibitory mode of binding with any of the substrates examined, activates only the hydrolysis of dipeptides by CPB, and has a greater effect on the hydrolysis of the basic dipeptide than on the neutral dipeptide. Moreover, when Bz-Gly-Lys is the substrate, cyclohexanol activates its hydrolysis by CPB by increasing both the enzyme–substrate binding affinity and the rate of the catalytic step, an effect different from that observed when Bz-Gly is the modifier.The anomalous kinetic behavior of CPB is remarkably similar to that of carboxypeptidase A, and is a good indication that both enzymes have very similar structures in and around their respective active sites. A binding site for activator molecules down the cleft of the active site is proposed for CPB to explain the observed kinetic behavior.

scholarly journals Enzymatic hydrolysis of oil palm empty fruit bunch to produce reducing sugar and its kinetic Hidrolisis enzimatik tandan kosong kelapa sawit untuk menghasilkan gula pereduksi dan kinetikanya

2016 ◽  
Vol 83 (1) ◽  
Author(s):  
Vera BARLIANTI ◽  
Deliana DAHNUM ◽  
. MURYANTO ◽  
Eka TRIWAHYUNI ◽  
Yosi ARISTIAWAN ◽  
...  
Keyword(s):  
Enzymatic Hydrolysis ◽  
Oil Palm ◽  
Volume Ratio ◽  
Enzyme Concentration ◽  
Reducing Sugar ◽  
Economic Feasibility ◽  
First Order ◽  
Empty Fruit Bunches ◽  
Hydrolysis Process ◽  
Hydrolysis Of

Abstrak Sebagai salah satu Negara penghasil minyak kelapa sawit mentah (CPO), Indonesia juga menghasilkan tandan kosong kelapa sawit (TKKS) dalam jumlah besar. TKKS terdiri dari-tiga-komponen utama, yaitu selulosa, hemiselulosa, dan lignin. Pengolahan awal TKKS secara alkalindi ikuti dengan hidrolisis TKKS secara enzimatik menggunakan kombinasi enzim selulase dan β-glukosidase akan menghasilkan gula-gula yang mudah difermentasi.  Penelitian ini bertujuan untuk mempelajari pengaruh konsentrasi substrat, kon-sentrasi enzim, dan suhu selama proses hidrolisis berlangsung.  Hasil yang diperoleh menunjukkan bahwa konsentrasi gula maksimum (194,78 g/L) dicapai pada konsentrasi TKKS 20% (b/v), konsentrasi campuran enzim yang terdiri dari selulase dan β-1,4 glukosidase sebesar 3,85% (v/v), dan suhu 50oC. Perbandingan antara selulase dan β-1,4 glukosidase adalah 5:1 dengan masing-masing aktivitas enzim sebesar 144.5 FPU/mL dan 63 FPU/mL. Hasil penelitian juga menunjukkan bahwa model kinetika yang sesuai untuk proses hidrolisis TKKS secara enzimatik adalah model kinetika Shen dan Agblevor dengan reakside aktivasi enzim orde satu.  Hasil ini mendukung studi kelayakan ekonomi dalam pemanfaatan TKKS untuk produksi bioetanol.AbstractAs one of the crude palm oil producers, Indonesia also produces empty fruit bunches (EFB)in large quantities. The oil palm EFB consist of cellulose, hemicellulose and lignin. Alkaline pretreatment of EFB, followed by enzymatic hydro-lysis of cellulose using combination of cellulase and β-glucosidase enzymes produce fermentable sugars. This paper reported the effects of substrate loading, enzyme concentration, and temperature of hydrolysis process on reducing sugar production. The  maximum  sugar  concentration (194.78 g/L) was produced at 50oC using 20% (w/v) EFB and 3.85% (v/v) mixed enzymes of cellulase and β-1,4 glucosidase in volume ratio of 5:1 (v/v), with enzyme activity of 144.5 FPU/mL and 63 FPU/mL, respectively. The results also showed that the suitable kinetic model for enzymatic hydrolysis process of oil palm EFB follow Shen and Agblevor model with first order of enzyme deactivation. These results support the economic feasibility study in utilization of EFB of oil palm for bioethanol production.    

scholarly journals A Degradation Product from Hydrolysate of Imipenem with Imis Broad-Spectrum Inhibits Metallo-β-Lactamases

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Ying Ge ◽  
Li-Wei Xu ◽  
Jian-Bin Zhen ◽  
Cheng Chen ◽  
Miao Lv ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Degradation Product ◽  
Substrate Inhibition ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Leaving Group ◽  
Ic50 Values ◽  
Hydrolysis Of

Background: Infections caused by metallo-β-lactamases (MβLs)-producing antibiotic-resistant bacteria pose a severe threat to public health. The synergistic use of current antibiotics in combination with MβL inhibitors is a promising therapeutic mode against these antibiotic-resistant bacteria. Objectives: The study aimed to probe the inhibition of MβLs and obtain the active component, P1, in the degradation product after imipenem was hydrolyzed by ImiS. Methods: The hydrolysis of two carbapenems with MβL ImiS was monitored by UV-Vis in real-time, and the degradation product from the leaving group produced after imipenem was hydrolyzed (but not for faropenem) was purified by HPLC to give one component, P1. Results: Kinetic assays revealed that P1 exhibited a broad-spectrum inhibition against VIM-2, NDM-1, ImiS, and L1, from three sub-classes of MβLs, with IC50 values of 8 - 32, 13.8 - 29.3, and 14.2 - 19.2 µM, using imipenem, cefazolin, and nitrocefin as substrates, respectively. Also, P1 showed synergistic antibacterial efficacy against drug-resistant Escherichia coli producing VIM-2, NDM-1, ImiS, and L1, in combination with antibiotics, restoring 16 to 32-fold and 32 to 128-fold efficacies of imipenem and cefazolin, respectively. Spectroscopic and Ellman's reagent analyses suggested that P1, a mercaptoethyl-form imidamide, is a mechanism-based inhibitor, while faropenem has no substrate inhibition, due to the lack of a leaving group. Conclusions: This work reveals that the hydrolysate of imipenem, a carbapenem with a good leaving group, can be used in screening for broad-spectrum inhibitors of MβLs.

Human cholinesterases

2020 ◽  
pp. 63-120
Author(s):  
Sergey Varfolomeev ◽  
Bella Grigorenko ◽  
Sofya Lushchekina ◽  
Alexander Nemuchin
Keyword(s):  
Active Site ◽  
The Body ◽  
Polymorphic Modification ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
Mechanism Of Hydrolysis ◽  
The Central Nervous System ◽  
The Stability ◽  
Hydrolysis Of ◽  
Enzyme Reactivity

The work is devoted to modeling the elementary stages of the hydrolysis reaction in the active site of enzymes belonging to the class of cholinesterases — acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The study allowed to describe at the molecular level the effect of the polymorphic modification of BChE, causing serious physiolog ical consequences. Cholinesterase plays a crucial role in the human body. AChE is one of the key enzymes of the central nervous system, and BChE performs protective functions in the body. According to the results of calculations using the combined method of quantum and molecular mechanics (KM/MM), the mechanism of the hydrolysis of the native acetylcholine substrate in the AChE active center was detailed. For a series of ester substrates, a method for estimation of dependence of the enzyme reactivity on the structure of the substrate has been developed. The mechanism of hydrolysis of the muscle relaxant of succininylcholine BChE and the effect of the Asp70Gly polymorph on it were studied. Using various computer simulation methods, the stability of the enzyme-substrate complex of two enzyme variants with succinylcholine was studied.

Heterobimetallische 3d-4f-Komplexe mit Bis(1,2-dithiooxalato)nickelat(II) als planarem Brückenbaustein / Heterobimetallic 3d-4f-Complexes with Bis(1,2-dithiooxalato)nickelate(II) as Planar Bridging Block

2005 ◽  
Vol 60 (11) ◽  
pp. 1149-1157 ◽  
Author(s):  
Matthias Siebold ◽  
Alexandra Kelling ◽  
Uwe Schilde ◽  
Peter Strauch
Keyword(s):  
Room Temperature ◽  
Magnetic Moments ◽  
Lanthanide Ions ◽  
Water Molecules ◽  
Unit Cell Parameters ◽  
Ionic Radii ◽  
X Ray ◽  
Cell Parameters ◽  
Heterobimetallic Complexes ◽  
The Individual

Planar bis(1,2-dithiooxalato)nickelates(II) react in aqueous solutions of lanthanide ions to form pentanuclear, heterobimetallic complexes of the general composition [{Ln(H2O)n}2- {Ni(dto)2}3]・xH2O (Ln = Y3+, La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+, Lu3+; n = 4 or 5; x = 9 - 12). With [{Nd(H2O)5}2{Ni(S2C2O2)2}3]・xH2O (x = 10 - 12) (1) and [{Er(H2O)4}2{Ni(S2C2O2)2}3]・xH2O (x = 9 - 10) (2) we were able to isolate two complexes of this series as single crystals, which were characterized by X-ray structure analysis. Depending on the individual ionic radii of the lanthanide ions, the compounds crystallize in two different crystal systems with the following unit cell parameters: 1, monoclinic in P21/c with a = 11.3987(13), b = 11.4878(8), c = 20.823(2) Å , β = 98.907(9)° and Z = 2; 2, triclinic in P1̅ with a = 10.5091(6), b = 11.0604(6), c = 11.2823(6) Å , α = 107.899(4)°, β = 91.436(4)°, γ = 112.918(4)° and Z = 1. The channels and cavities appearing in the packing of the molecules are occupied by uncoordinated water molecules. High magnetic moments up to 14.65 BM./f.u. have been observed at room temperature due to the combined moments of the individual lanthanide ions.

Sign in / Sign up

Export Citation Format

Share Document