当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > Plasminogen activator inhibitor-2 is highly tolerant to P8 residue substitution--implications for serpin mechanistic model and prediction of nsSNP activities.

Plasminogen activator inhibitor-2 is highly tolerant to P8 residue substitution--implications for serpin mechanistic model and prediction of nsSNP activities.

Abstract：

:The serine protease inhibitor (serpin) superfamily is involved in a wide range of cellular processes including fibrinolysis, angiogenesis, apoptosis, inflammation, metastasis and viral pathogenesis. Here, we investigate the unique mousetrap inhibition mechanism of serpins through saturation mutagenesis of the P8 residue for a typical family member, plasminogen activator inhibitor-2 (PAI-2). A number of studies have proposed an important role for the P8 residue in the efficient insertion and stabilisation of the cleaved reactive centre loop (RCL), which is a key event in the serpin inhibitory mechanism. The importance of this residue for inhibition of the PAI-2 protease target urinary plasminogen activator (urokinase, uPA) is confirmed, although a high degree of tolerance to P8 substitution is observed. Out of 19 possible PAI-2 P8 mutants, 16 display inhibitory activities within an order of magnitude of the wild-type P8 Thr species. Crystal structures of complexes between PAI-2 and RCL-mimicking peptides with P8 Met or Asp mutations are determined, and structural comparison with the wild-type complex substantiates the ability of the S8 pocket to accommodate disparate side-chains. These data indicate that the identity of the P8 residue is not a determinant of efficient RCL insertion, and provide further evidence for functional plasticity of key residues within enzyme structures. Poor correlation of observed PAI-2 P8 mutant activities with a range of physicochemical, evolutionary and thermodynamic predictive indices highlights the practical limitations of existing approaches to predicting the molecular phenotype of protein variants.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Di Giusto DA,Sutherland AP,Jankova L,Harrop SJ,Curmi PM,King GC

doi

10.1016/j.jmb.2005.09.008

keywords:

subject

Has Abstract

pub_date

2005-11-11 00:00:00

pages

1069-80

issue

5

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(05)01061-2

journal_volume

353

pub_type

杂志文章

相关文献

JOURNAL OF MOLECULAR BIOLOGY文献大全
  • Snapshots of RecA protein involving movement of the C-domain and different conformations of the DNA-binding loops: crystallographic and comparative analysis of 11 structures of Mycobacterium smegmatis RecA.

    abstract：:Mycobacterium smegmatis RecA and its nucleotide complexes crystallize in three different, but closely related, forms characterized by specific ranges of unit cell dimensions. The six crystals reported here and five reported earlier, all grown under the same or very similar conditions, belong to these three forms, all ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.01.058

    authors： Krishna R,Prabu JR,Manjunath GP,Datta S,Chandra NR,Muniyappa K,Vijayan M

    更新日期：2007-04-06 00:00:00

  • Coliphage P2 late control gene ogr. DNA sequence and product identification.

    abstract：:The bacteriophage P2 late control gene ogr was cloned and precisely localized by deletion analysis in vitro. The DNA sequence of the ogr gene containing the ogr1 mutation was determined. The sequence translates into a basic protein of a molecular weight of 8300. Plasmids overproducing the ogr gene product were constru...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(86)90170-1

    authors： Birkeland NK,Lindquist BH

    更新日期：1986-04-05 00:00:00

  • Crystal structure of the Vibrio cholerae cytolysin (VCC) pro-toxin and its assembly into a heptameric transmembrane pore.

    abstract：:Pathogenic Vibrio cholerae secrete V. cholerae cytolysin (VCC), an 80 kDa pro-toxin that assembles into an oligomeric pore on target cell membranes following proteolytic cleavage and interaction with cell surface receptors. To gain insight into the activation and targeting activities of VCC, we solved the crystal stru...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2005.05.045

    authors： Olson R,Gouaux E

    更新日期：2005-07-29 00:00:00

  • Three-dimensional structure of a cloning vector. X-ray diffraction studies of filamentous bacteriophage M13 at 7 A resolution.

    abstract：:Filamentous bacteriophage M13 is a single-stranded DNA phage about 65 A in diameter and 9300 A long. X-ray diffraction studies of magnetically oriented fibers of native, mercury and iodine-labeled phage particles have been used to determine the arrangement of the major coat protein, the gene 8 product, in the virion. ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(92)90960-r

    authors： Glucksman MJ,Bhattacharjee S,Makowski L

    更新日期：1992-07-20 00:00:00

  • Insertions of palindromic DNA sequences into the J-F intercistronic region of bacteriophage phi X174 interfere with normal phage growth.

    abstract：:The effect of hairpin (cruciform) size on the regulation of gene expression was investigated by cloning a series of palindromic sequences into the non-essential J-F intercistronic region of the bacteriophage phi X174 ins6 genome. Genetic stability of the insert sequence and its effect on the growth efficiency of the p...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(86)90510-3

    authors： Müller UR,Turnage MA

    更新日期：1986-05-20 00:00:00

  • Effect of the Asn52----Ile mutation on the redox potential of yeast cytochrome c. Theory and experiment.

    abstract：:Theoretical methods for correlation of sequence changes and redox potential of electron transport proteins are examined using the Asn52----Ile mutation in cytochrome c as a test case. The first approach uses the protein dipoles Langevin dipoles (PDLD) method and the high resolution X-ray structures of the native and t...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(92)90546-v

    authors： Langen R,Brayer GD,Berghuis AM,McLendon G,Sherman F,Warshel A

    更新日期：1992-04-05 00:00:00

  • Observing membrane protein diffusion at subnanometer resolution.

    abstract：:Single sodium-driven rotors from a bacterial ATP synthase were embedded into a lipid membrane and observed in buffer solution at subnanometer resolution using atomic force microscopy (AFM). Time-lapse AFM topographs show the movement of single proteins within the membrane. Subsequent analysis of their individual traje...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(03)00206-7

    authors： Müller DJ,Engel A,Matthey U,Meier T,Dimroth P,Suda K

    更新日期：2003-04-11 00:00:00

  • Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta.

    abstract：:The nuclear receptors peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the metabolic syndrome. Here, we show that they are direct regulators of the family of pyruvate dehydrogenase kinase (PDK) genes, whose products act as metabolic homeostats in sensing hunger and satiety level...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.06.091

    authors： Degenhardt T,Saramäki A,Malinen M,Rieck M,Väisänen S,Huotari A,Herzig KH,Müller R,Carlberg C

    更新日期：2007-09-14 00:00:00

  • An unusually long-lived antisense RNA in plasmid copy number control: in vivo RNAs encoded by the streptococcal plasmid pIP501.

    abstract：:The main regulator of pIP501 replication is an antisense RNA (RNAIII) that induces transcriptional attenuation of the essential RNAII. Previous studies identified the termination point in vivo and demonstrated attenuation in vitro. This in vivo analysis confirms the appearance of attenuated RNAII dependent on RNAIII. ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0023

    authors： Brantl S,Wagner EG

    更新日期：1996-01-19 00:00:00

  • Bypass of DNA heterologies during RuvAB-mediated three- and four-strand branch migration.

    abstract：:During general genetic recombination and recombinational DNA repair, DNA damages and heterologies are often encountered which must be efficiently processed by the cellular recombination machinery. In RecA-mediated three-strand exchange reactions between single-stranded circular and linear duplex DNA, or four-strand ex...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0600

    authors： Adams DE,West SC

    更新日期：1996-11-08 00:00:00

  • Titin organisation and the 3D architecture of the vertebrate-striated muscle I-band.

    abstract：:The giant muscle protein titin (connectin) is known to serve as a cytoskeletal element in muscle sarcomeres. It elastically restrains lengthening sarcomeres, it aids the integrity and central positioning of the A-band in the sarcomere and it may act as a template upon which some sarcomeric components are laid down dur...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(02)00819-7

    authors： Knupp C,Luther PK,Squire JM

    更新日期：2002-09-27 00:00:00

  • Solution Conformation of Bovine Leukemia Virus Gag Suggests an Elongated Structure.

    abstract：:Bovine leukemia virus (BLV) is a deltaretrovirus that infects domestic cattle. The structural protein Gag, found in all retroviruses, is a polyprotein comprising three major functional domains: matrix (MA), capsid (CA), and nucleocapsid (NC). Previous studies have shown that both mature BLV MA and NC are able to bind ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2019.01.036

    authors： Qualley DF,Cooper SE,Ross JL,Olson ED,Cantara WA,Musier-Forsyth K

    更新日期：2019-03-15 00:00:00

  • Structural and functional analyses of beta-glucosidase 3B from Thermotoga neapolitana: a thermostable three-domain representative of glycoside hydrolase 3.

    abstract：:Based on sequence and phylogenetic analyses, glycoside hydrolase (GH) family 3 can be divided into several clusters that differ in the length of their primary sequences. However, structural data on representatives of GH3 are still scarce, since only three of their structures are known and only one of them has been tho...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2010.01.072

    authors： Pozzo T,Pasten JL,Karlsson EN,Logan DT

    更新日期：2010-04-02 00:00:00

  • NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex.

    abstract：:We have determined, at high resolution, the NMR solution structure of an oxaliplatin-GG DNA dodecamer in the AGGC sequence context by 2D NMR studies. Homonuclear assignment strategies resulted in unambiguous assignment of 203 out of 249 protons, which corresponds to assignment of approximately 81% of the protons. Assi...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2004.06.066

    authors： Wu Y,Pradhan P,Havener J,Boysen G,Swenberg JA,Campbell SL,Chaney SG

    更新日期：2004-08-27 00:00:00

  • Transcription of the xyl operon is controlled in Bacillus subtilis by tandem overlapping operators spaced by four base-pairs.

    abstract：:The expression of xylose utilization in Bacillus subtilis is regulated at the level of transcription by xylose dependent Xyl repressor-xyl operator interaction. We have structurally and functionally characterized the binding sites of Xyl repressor in the xyl regulatory region. Methylation and hydroxyl radical protecti...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1994.1669

    authors： Dahl MK,Degenkolb J,Hillen W

    更新日期：1994-10-28 00:00:00

  • An examination of the electrostatic interactions between the N-terminal tail of the Brome Mosaic Virus coat protein and encapsidated RNAs.

    abstract：:The coat protein of positive-stranded RNA viruses often contains a positively charged tail that extends toward the center of the capsid and interacts with the viral genome. Electrostatic interaction between the tail and the RNA has been postulated as a major force in virus assembly and stabilization. The goal of this ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2012.03.023

    authors： Ni P,Wang Z,Ma X,Das NC,Sokol P,Chiu W,Dragnea B,Hagan M,Kao CC

    更新日期：2012-06-22 00:00:00

  • Increasing the thermostability of staphylococcal nuclease: implications for the origin of protein thermostability.

    abstract：:Seven hyper-stable multiple mutants have been constructed in staphylococcal nuclease by various combinations of eight different stabilizing single mutants. The stabilities of these multiple mutants determined by guanidine hydrochloride denaturation were 3.4 to 5.6 kcal/mol higher than that of the wild-type. Their ther...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2000.4140

    authors： Chen J,Lu Z,Sakon J,Stites WE

    更新日期：2000-10-20 00:00:00

  • The 0.93A crystal structure of sphericase: a calcium-loaded serine protease from Bacillus sphaericus.

    abstract：:We have previously isolated sphericase (Sph), an extracellular mesophilic serine protease produced by Bacillus sphaericus. The Sph amino acid sequence is highly homologous to two cold-adapted subtilisins from Antarctic bacilli S39 and S41 (76% and 74% identity, respectively). Sph is calcium-dependent, 310 amino acid r...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2003.07.011

    authors： Almog O,González A,Klein D,Greenblatt HM,Braun S,Shoham G

    更新日期：2003-10-03 00:00:00

  • Removal of a terminator structure by RNA processing regulates int gene expression.

    abstract：:The int gene of phage lambda encodes a protein involved in site-specific recombination. Its expression is regulated differentially during successive phases of the lambda infective cycle. The gene is transcribed early after infection from one promoter, pL, and later from a second promoter pI. Each transcription event r...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(84)90381-4

    authors： Schmeissner U,McKenney K,Rosenberg M,Court D

    更新日期：1984-06-15 00:00:00

  • Lattice models for proteins reveal multiple folding nuclei for nucleation-collapse mechanism.

    abstract：:The nature of the nucleation-collapse mechanism in protein folding is probed using 27-mer and 36-mer lattice models. Three different forms for the interaction potentials are used. Three of the four 27-mer sequences have maximally compact and identical native state while the other has a non-compact native conformation....

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.1997

    authors： Klimov DK,Thirumalai D

    更新日期：1998-09-18 00:00:00

  • Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties.

    abstract：:Pancreatic amyloid is found in more than 95 % of type II diabetes patients. Pancreatic amyloid is formed by the aggregation of islet amyloid polypeptide (hIAPP or amylin), which is a 37-residue peptide. Because pancreatic amyloid is cytotoxic, it is believed that its formation is directly associated with the developme...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1999.3422

    authors： Tenidis K,Waldner M,Bernhagen J,Fischle W,Bergmann M,Weber M,Merkle ML,Voelter W,Brunner H,Kapurniotu A

    更新日期：2000-01-28 00:00:00

  • IS1-mediated tandem duplication of plasmid pBR322. Dependence on recA and on DNA polymerase I.

    abstract：:Transposable-element-mediated fusion of the conjugal plasmid pOX38::Tn9 with pBR322 results in the appearance of cointegrates composed of a single copy of each plasmid, and cointegrates which carry a single copy of pOX38 but multiple tandem copies of pBR322. These plasmids are separated by directly repeated copies of ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/s0022-2836(83)80249-6

    authors： Chandler M,Galas DJ

    更新日期：1983-03-25 00:00:00

  • Reconstituted and native iron-cores of bacterioferritin and ferritin.

    abstract：:The structural and magnetic properties of the iron-cores of reconstituted horse spleen ferritin and Azotobacter vinelandii bacterioferritin have been investigated by high-resolution transmission electron microscopy, electron diffraction and Mossbauer spectroscopy. The structural properties of native horse spleen ferri...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(87)90290-7

    authors： Mann S,Williams JM,Treffry A,Harrison PM

    更新日期：1987-12-05 00:00:00

  • phi29 DNA polymerase active site: role of residue Val250 as metal-dNTP complex ligand and in protein-primed initiation.

    abstract：:DNA polymerases require two acidic residues to coordinate metal ions A and B at their polymerisation active site during catalysis of nucleotide incorporation. Crystallographic resolution of varphi29 DNA polymerase ternary complex showed that metal B coordination also depends on the carbonyl group of Val250 that belong...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2009.10.061

    authors： Pérez-Arnaiz P,Lázaro JM,Salas M,de Vega M

    更新日期：2010-01-15 00:00:00

  • Distribution of surface-exposed and non-accessible amino acid sequences among the two major structural domains of the S-layer protein of Aeromonas salmonicida.

    abstract：:The tetragonally arranged crystalline surface protein array (A-layer) of the fish pathogenic bacterium Aeromonas salmonicida is a virulence factor. Circular dichroism studies in the presence or absence of 0.1% sodium dodecyl sulfate showed that the secondary structure of A-protein, and its 39,439 molecular weight amin...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1993.1550

    authors： Doig P,McCubbin WD,Kay CM,Trust TJ

    更新日期：1993-10-20 00:00:00

  • Ribonucleoprotein complexes of R17 coat protein and a translational operator analog.

    abstract：:The coat protein of the simple spherical (triangulation no. T = 3) RNA coliphage R17 protects the genomic RNA in the virus particle and acts as a translational repressor of the phage-encoded replicase gene. It has been suggested that these two functions are related and that the translational repression complex serves ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(88)90052-6

    authors： Beckett D,Uhlenbeck OC

    更新日期：1988-12-20 00:00:00

  • Temperature-dependent dynamics of the villin headpiece helical subdomain, an unusually small thermostable protein.

    abstract：:(15)N spin relaxation experiments were used to measure the temperature-dependence of protein backbone conformational fluctuations in the thermostable helical subdomain, HP36, of the F-actin-binding headpiece domain of chicken villin. HP36 is the smallest domain of a naturally occurring protein that folds cooperatively...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/S0022-2836(02)00537-5

    authors： Vugmeyster L,Trott O,McKnight CJ,Raleigh DP,Palmer AG 3rd

    更新日期：2002-07-19 00:00:00

  • Crystallographic structure of phosphofructokinase-2 from Escherichia coli in complex with two ATP molecules. Implications for substrate inhibition.

    abstract：:Phosphofructokinase-1 and -2 (Pfk-1 and Pfk-2, respectively) from Escherichia coli belong to different homologous superfamilies. However, in spite of the lack of a common ancestor, they share the ability to catalyze the same reaction and are inhibited by the substrate MgATP. Pfk-2, an ATP-dependent 6-phosphofructokina...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.08.029

    authors： Cabrera R,Ambrosio AL,Garratt RC,Guixé V,Babul J

    更新日期：2008-11-14 00:00:00

  • Principles governing amino acid composition of integral membrane proteins: application to topology prediction.

    abstract：:A new method is suggested here for topology prediction of helical transmembrane proteins. The method is based on the hypothesis that the localizations of the transmembrane segments and the topology are determined by the difference in the amino acid distributions in various structural parts of these proteins rather tha...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.2107

    authors： Tusnády GE,Simon I

    更新日期：1998-10-23 00:00:00

  • Intriguing conformation changes associated with the trans/cis isomerization of a prolyl residue in the active site of the DsbA C33A mutant.

    abstract：:Escherichia coli DsbA belongs to the thioredoxin family and catalyzes the formation of disulfide bonds during the folding of proteins in the bacterial periplasm. It active site (C30-P31-H32-C33) consists of a disulfide bridge that is transferred to newly translocated proteins. The work reported here refers to the DsbA...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2005.01.049

    authors： Ondo-Mbele E,Vivès C,Koné A,Serre L

    更新日期：2005-04-01 00:00:00