当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > Molecular dynamics characterization of five pathogenic Factor X mutants associated with decreased catalytic activity.

Molecular dynamics characterization of five pathogenic Factor X mutants associated with decreased catalytic activity.

Abstract：

:Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Abdel-Azeim S,Oliva R,Chermak E,De Cristofaro R,Cavallo L

doi

10.1021/bi500770p

subject

Has Abstract

pub_date

2014-11-11 00:00:00

pages

6992-7001

issue

44

eissn

0006-2960

issn

1520-4995

journal_volume

53

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全
  • A theory of phase transitions and phase diagrams for one- and two-component phospholipid bilayers.

    abstract：:A statistical mechanical partition function for phospholipid bilayers is constructed to obtain a theoretical description of the chain melting phase transition in lipid bilayer membranes and of the phase diagrams for two-component bilayers. In addition to providing an accurate representation of the transition temperatu...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00639a004

    authors： Jacobs RE,Hudson BS,Andersen HC

    更新日期：1977-10-04 00:00:00

  • Conformational states of N-acylalanine dithio esters: correlation of resonance Raman spectra with structures.

    abstract：:The conformational states of N-acylalanine dithio esters, involving rotational isomers about the RC(=O)NH--CH(CH3) and NHCH(CH3)--C(=S) bonds, are defined and compared to those of N-acylglycine dithio esters. The structure of N-(p-nitrobenzoyl)-DL-alanine ethyl dithio ester has been determined by X-ray crystallographi...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00401a038

    authors： Lee H,Angus RH,Storer AC,Varughese KI,Carey PR

    更新日期：1988-01-12 00:00:00

  • Structural basis for hydration dynamics in radical stabilization of bilin reductase mutants.

    abstract：:Heme-derived linear tetrapyrroles (phytobilins) in phycobiliproteins and phytochromes perform critical light-harvesting and light-sensing roles in oxygenic photosynthetic organisms. A key enzyme in their biogenesis, phycocyanobilin:ferredoxin oxidoreductase (PcyA), catalyzes the overall four-electron reduction of bili...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi100728q

    authors： Kohler AC,Gae DD,Richley MA,Stoll S,Gunn A,Lim S,Martin SS,Doukov TI,Britt RD,Ames JB,Lagarias JC,Fisher AJ

    更新日期：2010-07-27 00:00:00

  • Mutation of Arg-166 of alkaline phosphatase alters the thio effect but not the transition state for phosphoryl transfer. Implications for the interpretation of thio effects in reactions of phosphatases.

    abstract：:It has been suggested that the mechanism of alkaline phosphatase (AP) is associative, or triester-like, because phosphorothioate monoesters are hydrolyzed by AP approximately 10(2)-fold slower than phosphate monoesters. This "thio effect" is similar to that observed for the nonenzymatic hydrolysis of phosphate trieste...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi000899x

    authors： Holtz KM,Catrina IE,Hengge AC,Kantrowitz ER

    更新日期：2000-08-08 00:00:00

  • Inhibition of phosphomannose isomerase by mercury ions.

    abstract：:Mercury ions can inhibit Candida albicans phosphomannose isomerase (PMI) by two different processes at sub-micromolar concentrations. Kinetic studies show that mercury ions are in rapid equilibrium with the enzyme and cause a clear partial noncompetitive inhibition when mannose 6-phosphate is used as the substrate. Th...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00190a018

    authors： Wells TN,Payton MA,Proudfoot AE

    更新日期：1994-06-21 00:00:00

  • Glycosylation of natural human neutrophil gelatinase B and neutrophil gelatinase B-associated lipocalin.

    abstract：:Gelatinase B is a matrix metalloproteinase (MMP-9) involved in tissue remodeling, development, cancer, and inflammation. Neutrophils produce three major forms of (pro)gelatinase B: 92 kDa monomers, homodimers, and complexes of gelatinase B covalently bound to neutrophil gelatinase B-associated lipocalin (NGAL). In con...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi991162e

    authors： Rudd PM,Mattu TS,Masure S,Bratt T,Van den Steen PE,Wormald MR,Küster B,Harvey DJ,Borregaard N,Van Damme J,Dwek RA,Opdenakker G

    更新日期：1999-10-19 00:00:00

  • Incorporation of fragment X into fibrin clots renders them more susceptible to lysis by plasmin.

    abstract：:Bleeding, the most serious complication of thrombolytic therapy with tissue-type plasminogen activator (t-PA), is thought to result from lysis of fibrin in hemostatic plugs and from the systemic lytic state caused by unopposed plasmin. One mechanism by which systemic plasmin can impair hemostasis is by partially degra...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi0525730

    authors： Schaefer AV,Leslie BA,Rischke JA,Stafford AR,Fredenburgh JC,Weitz JI

    更新日期：2006-04-04 00:00:00

  • Titration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N-myristoyltransferase.

    abstract：:Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase (Nmt1p) is an essential enzyme that catalyzes the transfer of myristic acid (C14:0) from myristoylCoA to the N-terminus of cellular proteins with a variety of functions. Nmts from an assortment of species display remarkable in vivo specificity for th...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi970311v

    authors： Bhatnagar RS,Schall OF,Jackson-Machelski E,Sikorski JA,Devadas B,Gokel GW,Gordon JI

    更新日期：1997-06-03 00:00:00

  • Location of sites in human lipocortin I that are phosphorylated by protein tyrosine kinases and protein kinases A and C.

    abstract：:Lipocortin I is a 39-kilodalton membrane-associated protein that in A431 cells is phosphorylated on tyrosine in response to epidermal growth factor (EGF). We have used recombinant human lipocortin I as a substrate for several protein kinases and identified phosphorylated residues by a combination of peptide mapping an...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00410a024

    authors： Varticovski L,Chahwala SB,Whitman M,Cantley L,Schindler D,Chow EP,Sinclair LK,Pepinsky RB

    更新日期：1988-05-17 00:00:00

  • Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes.

    abstract：:ALY is a ubiquitously expressed nuclear protein which interacts with proteins such as TAP that are involved in export of mRNA from the nucleus to the cytoplasm, as well as with proteins that bind the T cell receptor alpha gene enhancer. ALY has also been shown to bind mRNA and to co-localize in the nucleus with compon...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi034062o

    authors： Pérez-Alvarado GC,Martínez-Yamout M,Allen MM,Grosschedl R,Dyson HJ,Wright PE

    更新日期：2003-06-24 00:00:00

  • Subunit affinities and stoichiometries of the human papillomavirus type 11 E1:E2:DNA complex.

    abstract：:The association between the papillomavirus E1 and E2 proteins is an important regulatory interaction, imparting coordinated control of viral transcription and replication. Using fluorescence polarization, we have characterized the interactions between HPV-11 E1, HPV-11 E2, and DNA in solution at equilibrium. For these...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi982616v

    authors： Chao SF,Rocque WJ,Daniel S,Czyzyk LE,Phelps WC,Alexander KA

    更新日期：1999-04-06 00:00:00

  • Solution structure of the actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2).

    abstract：:The solution structure of the actinorhodin acyl carrier protein (act apo-ACP) from the polyketide synthase (PKS) of Streptomyces coelicolor A3(2) has been determined using 1H NMR spectroscopy, representing the first polyketide synthase component for which detailed structural information has been obtained. Twenty-four ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi970006+

    authors： Crump MP,Crosby J,Dempsey CE,Parkinson JA,Murray M,Hopwood DA,Simpson TJ

    更新日期：1997-05-20 00:00:00

  • Engineering the independent folding of the subtilisin BPN' pro-domain: correlation of pro-domain stability with the rate of subtilisin folding.

    abstract：:The 77-amino acid pro-domain greatly accelerates the in vitro folding of subtilisin in a bimolecular reaction whose product is a tight complex between folded subtilisin and folded pro-domain. In this complex the pro-domain has a compact structure with a four-stranded antiparallel beta-sheet and two three-turn alpha-he...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi972741r

    authors： Wang L,Ruan B,Ruvinov S,Bryan PN

    更新日期：1998-03-03 00:00:00

  • Isolation and structure of a cross-linked tripeptide from calf bone collagen.

    abstract：:A cross-linked tripeptide has been isolated from alkaline hydrolysates of NaB3H4-reduced calf bone collagen. The peptide contains dihydroxylysinonorleucine, the most abundant cross-link in bone collagen, and it has a single N-terminal proline and a single C-terminal valine. These amino acids are in peptide linkage wit...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00691a011

    authors： Fujii K,Corcoran D,Tanzer ML

    更新日期：1975-10-07 00:00:00

  • Solid-State Nuclear Magnetic Resonance Structural Study of the Retinal-Binding Pocket in Sodium Ion Pump Rhodopsin.

    abstract：:The recently identified Krokinobacter rhodopsin 2 (KR2) functions as a light-driven sodium ion pump. The structure of the retinal-binding pocket of KR2 offers important insights into the mechanisms of KR2, which has motif of Asn112, Asp116, and Gln123 (NDQ) that is common among sodium ion pump rhodopsins but is unique...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.6b00999

    authors： Shigeta A,Ito S,Inoue K,Okitsu T,Wada A,Kandori H,Kawamura I

    更新日期：2017-01-31 00:00:00

  • The carboxy terminus of sodium and potassium ion transporting ATPase is located on the cytoplasmic surface of the membrane.

    abstract：:The positions, with respect to the plasma membrane, of lysine 905, contained in the peptide QRKIVE, and of lysine 1012, contained in the carboxy-terminal peptide, RPGGWVEKETYY, of ovine Na+/K(+)-transporting ATPase have been reported to be cytoplasmic and extracytoplasmic, respectively [Bayer, R. (1990) Biochemistry 2...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00062a012

    authors： Thibault D

    更新日期：1993-03-23 00:00:00

  • Calorimetric studies of adenosine 5'-triphosphate hydrolysis by heavy meromyosin.

    abstract：:The heat production for the reaction steps of ATP hydrolysis by heavy meromyosin has been reexamined by using a reaction-type calorimeter. So far, the values reported for the heat production have varied substantially among research groups. The present results obtained in 0.3 M KCl, 10 mM MgCl2, and 20 mM Tris-HCl at p...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00518a037

    authors： Yamada T,Shimizu H,Suga H

    更新日期：1981-07-21 00:00:00

  • Synthesis and characterization of fluorescently labeled bovine brain G protein subunits.

    abstract：:G proteins play an important role in transmitting hormonal signals, and fluorescence techniques would be useful to study their cellular distribution and mechanisms. To prepare active fluorescent G protein Go/Gi or beta gamma subunits were reacted with fluorescein isothiocyanate (FITC) to label the alpha (F-alpha) and ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00060a035

    authors： Kwon G,Remmers AE,Datta S,Neubig RR

    更新日期：1993-03-09 00:00:00

  • Bilayer interactions of ether- and ester-linked phospholipids: dihexadecyl- and dipalmitoylphosphatidylcholines.

    abstract：:Mixed phospholipid systems of ether-linked 1,2-dihexadecylphosphatidylcholine (DHPC) and ester-linked 1,2-dipalmitoylphosphatidylcholine (DPPC) have been studied by differential scanning calorimetry and X-ray diffraction. At maximum hydration (60 wt % water), DHPC shows three reversible transitions: a main (chain melt...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00395a006

    authors： Kim JT,Mattai J,Shipley GG

    更新日期：1987-10-20 00:00:00

  • Chiral sulfoxidations catalyzed by rat liver cytochromes P-450.

    abstract：:The chirality of sulfoxidation catalyzed by two cytochrome P-450 isozymes purified from phenobarbital-induced rat liver was studied by using 4-tolyl ethyl sulfide as a substrate. Both P-450 isoenzymes, termed PB-1 and PB-4, when reconstituted with purified rat liver NADPH-cytochrome P-450 reductase and cytochrome b5, ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00539a032

    authors： Waxman DJ,Light DR,Walsh C

    更新日期：1982-05-11 00:00:00

  • Lysine-146 of rabbit muscle aldolase is essential for cleavage and condensation of the C3-C4 bond of fructose 1,6-bis(phosphate).

    abstract：:Lysine-146 of rabbit muscle aldolase (D-fructose-1,6-biphosphate aldolase, EC 4.1.2.13) is absolutely conserved in class I (Schiff base) aldolases and has been implicated previously in catalysis by protein modification. Site-directed mutagenesis was used to change lysine-146 to alanine, glutamine, leucine, or histidin...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00206a036

    authors： Morris AJ,Tolan DR

    更新日期：1994-10-11 00:00:00

  • Multiple-ligand binding in CYP2A6: probing mechanisms of cytochrome P450 cooperativity by assessing substrate dynamics.

    abstract：:The contribution of ligand dynamics to CYP allosterism has not been considered in detail. On the basis of a previous study, we hypothesized that CYP2A6 and CYP2E1 accommodate multiple xylene ligands. As a result, the intramolecular ( k H/ k D) obs values observed for some xylene isomers are expected to be dependent on...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi702020y

    authors： Harrelson JP,Atkins WM,Nelson SD

    更新日期：2008-03-04 00:00:00

  • Pressure effects and thermal stability of myosin rods and rod minifilaments: fluorescence and circular dichroism studies.

    abstract：:In the present study hydrostatic pressure was applied upon both skeletal myosin rod molecules and rod minifilaments to learn more of the intra- and intermolecular interaction behavior of myosin. Applied pressure disassembled the rod minifilaments into individual rod molecules and dissociated each myosin rod molecule i...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00184a028

    authors： King L,Liu CC,Lee RF

    更新日期：1994-05-10 00:00:00

  • The Asp285 variant of DNA polymerase beta extends mispaired primer termini via increased nucleotide binding.

    abstract：:Endogenous DNA damage occurs at a rate of at least 20,000 lesions per cell per day. Base excision repair (BER) is a key pathway for maintaining genome stability. Several pol beta variants were identified as conferring resistance to 3'-azido-3'-deoxythymidine (AZT) in Escherichia coli (Kosa et al. (1999) J. Biol. Chem....

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi702104y

    authors： Murphy DL,Kosa J,Jaeger J,Sweasy JB

    更新日期：2008-08-05 00:00:00

  • Dynamic and equilibrium studies on the interaction of Ran with its effector, RanBP1.

    abstract：:Ran, a small nuclear GTP-binding protein, is one of the most abundant Ras-related proteins in eucaryotic cells. Ran is essential for nucleo-cytoplasmatic transport and is primarily localized in the nucleus and at the nuclear pore complex. Here, we characterize the kinetics and equilibrium of the interaction between Ra...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi970524k

    authors： Kuhlmann J,Macara I,Wittinghofer A

    更新日期：1997-10-07 00:00:00

  • Spectroscopic and kinetic studies of lipases solubilized in reverse micelles.

    abstract：:The conformation and activity of three different lipases have been studied in reverse micelles formed by sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in isooctane. In the case of human pancreatic lipase, the conformation of the polypeptide chain--as judged from far-UV circular dichroism measurements--is only slightly...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00066a025

    authors： Walde P,Han D,Luisi PL

    更新日期：1993-04-20 00:00:00

  • Perturbing the water cavity surrounding the manganese cluster by mutating the residue D1-valine 185 has a strong effect on the water oxidation mechanism of photosystem II.

    abstract：:The active site of water oxidation in Photosystem II (PSII) is a Mn4CaO5 cluster that is located in a cavity between the D1 and CP43 protein subunits by which it is coordinated. The remainder of this cavity is filled with water molecules, which serve as a source of substrate and participate in poorly understood hydrog...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi400930g

    authors： Dilbeck PL,Bao H,Neveu CL,Burnap RL

    更新日期：2013-10-01 00:00:00

  • Influence of the calcium-induced gel phase on the behavior of small molecules in phosphatidylserine and phosphatidylserine-phosphatidylcholine multilamellar vesicles.

    abstract：:The behavior of fluorescent and spin-label probes is examined in several fluid and gel phospholipid phases, with particular focus on the Ca2+-induced gel phase in phosphatidylserine (PS). These probes have behavior characteristic of the type of probe and of the type of lipid environment. Anthroyloxy- and doxyl-labeled...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00380a039

    authors： Florine KI,Feigenson GW

    更新日期：1987-03-24 00:00:00

  • Analysis of the structural core of the human estrogen receptor ligand binding domain by selective proteolysis/mass spectrometric analysis.

    abstract：:The structure of the ca. 250 amino acid hormone binding domain of the human estrogen receptor (hER-LBD), expressed in E. coli and purified as a complex with estradiol, has been probed by selective proteolysis, with analysis of the protein fragments both by classical methods (SDS-PAGE and Edman N-terminal sequencing) a...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00039a016

    authors： Seielstad DA,Carlson KE,Kushner PJ,Greene GL,Katzenellenbogen JA

    更新日期：1995-10-03 00:00:00

  • High-resolution solution structure of the EGF-like domain of heregulin-alpha.

    abstract：:The solution structure of the 63-residue heregulin-alpha (HRG-alpha) epidermal growth factor (EGF)-like domain, corresponding to residues 177-239 of HRG-alpha, has been determined to high resolution using data from two-dimensional and three-dimensional homo- and heteronuclear NMR spectroscopy. The structure is based o...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi952626l

    authors： Jacobsen NE,Abadi N,Sliwkowski MX,Reilly D,Skelton NJ,Fairbrother WJ

    更新日期：1996-03-19 00:00:00