Distal regulation of heme binding of heme oxygenase-1 mediated by conformational fluctuations.


:Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the oxidative degradation of heme. Since free heme is toxic to cells, rapid degradation of heme is important for maintaining cellular health. There have been useful mechanistic studies of the HO reaction based on crystal structures; however, how HO-1 recognizes heme is not completely understood because the crystal structure of heme-free rat HO-1 lacks electron densities for A-helix that ligates heme. In this study, we characterized conformational dynamics of HO-1 using NMR to elucidate the mechanism by which HO-1 recognizes heme. NMR relaxation experiments showed that the heme-binding site in heme-free HO-1 fluctuates in concert with a surface-exposed loop and transiently forms a partially unfolded structure. Because the fluctuating loop is located over 17 Å distal from the heme-binding site and its conformation is nearly identical among different crystal structures including catalytic intermediate states, the function of the loop has been unexamined. In the course of elucidating its function, we found interesting mutations in this loop that altered activity but caused little change to the conformation. The Phe79Ala mutation in the loop changed the conformational dynamics of the heme-binding site. Furthermore, the heme binding kinetics of the mutant was slower than that of the wild type. Hence, we concluded that the distal loop is involved in the regulation of the conformational change for heme binding through the conformational fluctuations. Similar to other enzymes, HO-1 effectively promotes its function using the identified distal sites, which might be potential targets for protein engineering.






Harada E,Sugishima M,Harada J,Fukuyama K,Sugase K




Has Abstract


2015-01-20 00:00:00












  • Nucleotide Excision Repair and Impact of Site-Specific 5',8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes.

    abstract::The nonbulky 5',8-cyclopurine DNA lesions (cP) and the bulky, benzo[ a]pyrene diol epoxide-derived stereoisomeric cis- and trans- N2-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad ...


    pub_type: 杂志文章


    authors: Shafirovich V,Kolbanovskiy M,Kropachev K,Liu Z,Cai Y,Terzidis MA,Masi A,Chatgilialoglu C,Amin S,Dadali A,Broyde S,Geacintov NE

    更新日期:2019-02-12 00:00:00

  • Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease.

    abstract::Snapshots of three consecutive steps in the proteolytic reaction of HIV-1 protease (PR) were obtained in crystal structures at resolutions of 1.2-1.4 Å. Structures of wild-type protease and two mutants (PR(V32I) and PR(I47V)) with V32I and I47V substitutions, which are common in drug resistance, reveal the gem-diol te...


    pub_type: 杂志文章


    authors: Shen CH,Tie Y,Yu X,Wang YF,Kovalevsky AY,Harrison RW,Weber IT

    更新日期:2012-10-02 00:00:00

  • Metal ion catalysis of RNA cleavage by the influenza virus endonuclease.

    abstract::The influenza virus RNA-dependent RNA polymerase protein complex contains an associated RNA endonuclease activity, which cleaves host mRNA precursors in the cell nucleus at defined positions 9-15 nucleotides downstream of the cap structure. This reaction provides capped oligoribonucleotides, which function as primers ...


    pub_type: 杂志文章


    authors: Doan L,Handa B,Roberts NA,Klumpp K

    更新日期:1999-04-27 00:00:00

  • A Novel Mechanism for Calmodulin-Dependent Inactivation of Transient Receptor Potential Vanilloid 6.

    abstract::The paralogues TRPV5 and TRPV6 belong to the vanilloid subfamily of the transient receptor potential (TRP) superfamily of ion channels, and both play an important role in overall Ca2+ homeostasis. The functioning of the channels centers on a tightly controlled Ca2+-dependent feedback mechanism in which the direct bind...


    pub_type: 杂志文章


    authors: Bate N,Caves RE,Skinner SP,Goult BT,Basran J,Mitcheson JS,Vuister GW

    更新日期:2018-05-08 00:00:00

  • Study of the conformational transition of A beta(1-42) using D-amino acid replacement analogues.

    abstract::A critical event in Alzheimer's disease is the transition of Abeta peptides from their soluble forms into disease-associated beta-sheet-rich conformers. Structural analysis of a complete D-amino acid replacement set of Abeta(1-42) enabled us to localize in the full-length 42-mer peptide the region responsible for the ...


    pub_type: 杂志文章


    authors: Janek K,Rothemund S,Gast K,Beyermann M,Zipper J,Fabian H,Bienert M,Krause E

    更新日期:2001-05-08 00:00:00

  • Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain.

    abstract::Isoforms of transforming growth factor beta (TGFbeta) are 25 kDa homodimeric polypeptides that signal by binding and bringing together two related, functionally distinct cell surface receptors designated as TbetaR1 and TbetaR2. Here, we report the solution structure of the 13.8 kDa extracellular domain of human TbetaR...


    pub_type: 杂志文章


    authors: Deep S,Walker KP 3rd,Shu Z,Hinck AP

    更新日期:2003-09-02 00:00:00

  • Molecular Basis for Allosteric Inhibition of GTP-Bound H-Ras Protein by a Small-Molecule Compound Carrying a Naphthalene Ring.

    abstract::The ras oncogene products (H-Ras, K-Ras, and N-Ras) have been regarded as some of the most promising targets for anticancer drug discovery because their activating mutations are frequently found in human cancers. Nonetheless, molecular targeted therapy for them is currently unavailable. Here, we report the discovery o...


    pub_type: 杂志文章


    authors: Matsumoto S,Hiraga T,Hayashi Y,Yoshikawa Y,Tsuda C,Araki M,Neya M,Shima F,Kataoka T

    更新日期:2018-09-11 00:00:00

  • Resonance Raman spectroscopy of squid and bovine visual pigments: the primary photochemistry in visual transduction.

    abstract::Resonance Raman spectra of squid rhodopsin have been obtained under a variety of temperature and illumination conditions. The data have been characterized in terms of spectral contributions from squid rhodopsin, isorhodopsin, bathorhodopsin, lumirhodopsin, mesorhodopsin, P-465, and acid metarhodopsin. The results are ...


    pub_type: 杂志文章


    authors: Sulkes M,Lewis A,Marcus MA

    更新日期:1978-10-31 00:00:00

  • Antisera specific for the alpha 1, alpha 2, alpha 3, and beta subunits of the Na,K-ATPase: differential expression of alpha and beta subunits in rat tissue membranes.

    abstract::We have developed a panel of antibodies specific for the alpha 1, alpha 2, alpha 3, and beta subunits of the rat Na,K-ATPase. TrpE-alpha subunit isoform fusion proteins were used to generate three antisera, each of which reacted specifically with a distinct alpha subunit isotype. Western blot analysis of rat tissue mi...


    pub_type: 杂志文章


    authors: Shyjan AW,Levenson R

    更新日期:1989-05-30 00:00:00

  • “Locked onto the target”: increasing the efficiency of antagomirzymes using locked nucleic acid modifications.

    abstract::This study highlights the effect of incorporation of locked nucleic acid (LNA) on improving the functional efficacy of DNAzymes against microRNAs (antagomirzymes). DNAzymes were designed against two different sites of miR-27a, which were encompassed both within the precursor and mature form of miRNA. The cleavage and ...


    pub_type: 杂志文章


    authors: Kaur H,Scaria V,Maiti S

    更新日期:2010-11-09 00:00:00

  • A transition path ensemble study reveals a linchpin role for Mg(2+) during rate-limiting ADP release from protein kinase A.

    abstract::Protein kinases are key regulators of diverse signaling networks critical for growth and development. Protein kinase A (PKA) is an important kinase prototype that phosphorylates protein targets at Ser and Thr residues by converting ATP to ADP. Mg(2+) ions play a crucial role in regulating phosphoryl transfer and can l...


    pub_type: 杂志文章


    authors: Khavrutskii IV,Grant B,Taylor SS,McCammon JA

    更新日期:2009-12-08 00:00:00

  • Direct electrochemistry of protein-protein complexes involving cytochrome c, cytochrome b5, and plastocyanin.

    abstract::The direct electrochemistry of the cytochrome c/cytochrome b5 and cytochrome c/plastocyanin complexes has been investigated at edge-plane graphite and modified gold electrode surfaces, which are selective for one of the two components of the complex. Electrochemical response of one protein at an otherwise electrostati...


    pub_type: 杂志文章


    authors: Bagby S,Barker PD,Guo LH,Hill HA

    更新日期:1990-04-03 00:00:00

  • Synthetic charybdotoxin-iberiotoxin chimeric peptides define toxin binding sites on calcium-activated and voltage-dependent potassium channels.

    abstract::Charybdotoxin (ChTX) and iberiotoxin (IbTX) are highly charged peptidyl toxins which exhibit 68% sequence identity and share a similar three-dimensional structure. Despite these structural similarities, IbTX and ChTX differ in their selectivity for two types of potassium channels; large conductance calcium-activated p...


    pub_type: 杂志文章


    authors: Giangiacomo KM,Sugg EE,Garcia-Calvo M,Leonard RJ,McManus OB,Kaczorowski GJ,Garcia ML

    更新日期:1993-03-09 00:00:00

  • Fitting the Pieces of the β-Barrel Assembly Machinery Complex.

    abstract::β-Barrel membrane proteins are found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria; however, exactly how they are folded and inserted remains unknown. Over the past decade, both functional and structural studies have greatly contributed to addressing this elusive mechanism. It is kno...


    pub_type: 杂志文章,评审


    authors: O'Neil PK,Rollauer SE,Noinaj N,Buchanan SK

    更新日期:2015-10-20 00:00:00

  • Role of juxtamembrane and transmembrane domains in the mechanism of natriuretic peptide receptor A activation.

    abstract::Natriuretic peptide receptor A (NPRA) is a noncovalent homodimeric receptor, composed of an extracellular domain (ECD) with a ligand-binding site, a single transmembrane domain (TM), and an intracellular domain (ICD) exhibiting guanylyl cyclase activity. NPRA activation by atrial natriuretic peptide (ANP) leads to cGM...


    pub_type: 杂志文章


    authors: Parat M,Blanchet J,De Léan A

    更新日期:2010-06-08 00:00:00

  • Ivermectin and nodulisporic acid receptors in Drosophila melanogaster contain both gamma-aminobutyric acid-gated Rdl and glutamate-gated GluCl alpha chloride channel subunits.

    abstract::35S-labeled derivatives of the insecticides nodulisporic acid and ivermectin were synthesized and demonstrated to bind with high affinity to a population of receptors in Drosophila head membranes that were previously shown to be associated with a glutamate-gated chloride channel. Nodulisporic acid binding was modeled ...


    pub_type: 杂志文章


    authors: Ludmerer SW,Warren VA,Williams BS,Zheng Y,Hunt DC,Ayer MB,Wallace MA,Chaudhary AG,Egan MA,Meinke PT,Dean DC,Garcia ML,Cully DF,Smith MM

    更新日期:2002-05-21 00:00:00

  • Affinity selection of chemically modified proteins: role of lysyl residues in the binding of calmodulin to calcineurin.

    abstract::In affinity selection, calcineurin selects from a population of randomly modified calmodulins those species with which it prefers to interact. The method shows that acetylation of lysines affects calmodulin so as to interfere with its ability to interact with calcineurin. Monoacetylation of any lysine of calmodulin re...


    pub_type: 杂志文章


    authors: Manalan AS,Klee CB

    更新日期:1987-03-10 00:00:00

  • Translational control of gene expression in a normal fibroblast. Characterization of a subclass of mRNAs with unusual kinetic properties.

    abstract::The translation of a small number of mRNAs in mouse SC-1 fibroblasts can be stimulated by cycloheximide, under conditions where the synthesis of most proteins is inhibited. These mRNAs are ordinarily present in small polyribosomes or messenger ribonucleoprotein particles, although the addition of cycloheximide drives ...


    pub_type: 杂志文章


    authors: Walden WE,Thach RE

    更新日期:1986-04-22 00:00:00

  • The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions.

    abstract::DNA gyrase and topoisomerase IV (Topo IV) are cellular targets of quinolone antibacterial drugs. The Ser-80 and the Glu-84 of the ParC subunit have been identified as mutational hotspots for quinolone resistance. Mutant Topo IV proteins containing a quinolone resistance-conferring mutation have been constructed, and t...


    pub_type: 杂志文章


    authors: Hiasa H

    更新日期:2002-10-01 00:00:00

  • Orientation and motion of spin-labels in rabbit small intestinal brush border vesicle membranes.

    abstract::The temperature dependence of the packing (order) and fluidity (microviscosity) of rabbit small, intestinal brush border vesicle membranes and of liposomes made from their extracted lipids has been investigated by using a variety of lipid spin probes. The lipids in the brush border membrane are present essentially as ...


    pub_type: 杂志文章


    authors: Hauser H,Gains N,Semenza G,Spiess M

    更新日期:1982-10-26 00:00:00

  • A probe of the active site acidity of carboxypeptidase A.

    abstract::The substrate analogue 2-(1-carboxy-2-phenylethyl)-4-phenylazophenol is a potent competitive inhibitor of carboxypeptidase A. Upon ligation to the active site, the azophenol moiety undergoes a shift of pKa from a value of 8.76 to a value of 4.9; this provides an index of the Lewis acidity of the active site zinc ion. ...


    pub_type: 杂志文章


    authors: Mock WL,Tsay JT

    更新日期:1986-05-20 00:00:00

  • Orientation and penetration depth of monolayer-bound p40phox-PX.

    abstract::X-ray reflectivity was used to study the interaction of the PX domain of p40(phox) protein (p40(phox)-PX) with a Langmuir monolayer of a mixture of SOPC (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine), SOPS (1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine), and DPPtdIns(3)P (1,2-dipalmitoylphosphatidylinositol 3-phos...


    pub_type: 杂志文章


    authors: Málková S,Stahelin RV,Pingali SV,Cho W,Schlossman ML

    更新日期:2006-11-14 00:00:00

  • The Interaction between the Third Type III Domain from Fibronectin and Anastellin Involves β-Strand Exchange.

    abstract::Anastellin is a small recombinant fragment derived from the extracellular matrix protein fibronectin; it comprises the first type III (FN3) domain without the two N-terminal β-strands. It inhibits angiogenesis, tumor growth, and metastasis in mouse models and requires endogenous fibronectin for its in vivo anti-angiog...


    pub_type: 杂志文章


    authors: Stine JM,Ahl GJH,Schlenker C,Rusnac DV,Briknarová K

    更新日期:2017-09-05 00:00:00

  • Molecular cloning of bovine cardiac muscle heat-shock protein 70 kDa and its phosphorylation by cAMP-dependent protein kinase in vitro.

    abstract::The 70-kDa heat-shock protein (Hsp70) has been cloned and sequenced from bovine cardiac muscle. On the basis of sequence features, the gene corresponds to the cytoplasmic form of Hsp70. This cardiac Hsp70 cDNA clone has an open reading frame of 1926 bp coding for 641 amino acids and a predicted molecular mass of 70.25...


    pub_type: 杂志文章


    authors: Lakshmikuttyamma A,Selvakumar P,Anderson DH,Datla RS,Sharma RK

    更新日期:2004-10-26 00:00:00

  • Diazomethyl ketone substrate derivatives as active-site-directed inhibitors of thiol proteases. Papain.

    abstract::The diazomethyl ketones of z-Phe-Phe inactivate papain by a stoichiometric reaction at the active-center thiol. Since the reagents are stable in mercaptoethanol, their reaction with papain is judged to be the result of complex formation characteristic of affinity-labeling reagents. The diazomethyl ketones react by a m...


    pub_type: 杂志文章


    authors: Leary R,Larsen D,Watanabe H,Shaw E

    更新日期:1977-12-27 00:00:00

  • Ethidium bromide complexes with self-complementary deoxytetranucleotides. Demonstration and discussion of sequence preferences in the intercalative binding of ethidium bromide.

    abstract::The binding of ethidium bromide to the self-complementary deoxytetranucleotides containing guanine and cytosine bases has been studied by circular dichroism, visible absorption, and fluorescence spectroscopies. The circular dichroism spectrum of each of the four deoxytetranucleotides was measured and compared to the s...


    pub_type: 杂志文章


    authors: Kastrup RV,Young MA,Krugh TR

    更新日期:1978-11-14 00:00:00

  • Structural and functional properties of human hemoglobins reassembled after synthesis in Escherichia coli.

    abstract::Human hemoglobin produced in the Escherichia coli coexpression system of Hernan et al. [(1992) Biochemistry 31, 8619-8628] has been transformed into a functionally homogeneous protein whose properties closely approximate those of normal hemoglobin A. Both of the alpha and beta chains of this hemoglobin contain a valin...


    pub_type: 杂志文章


    authors: Hui HL,Kavanaugh JS,Doyle ML,Wierzba A,Rogers PH,Arnone A,Holt JM,Ackers GK,Noble RW

    更新日期:1999-01-19 00:00:00

  • Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins.

    abstract::2-Cys peroxiredoxins (Prxs) are a large and diverse family of peroxidases which, in addition to their antioxidant functions, regulate cell signaling pathways, apoptosis, and differentiation. These enzymes are obligate homodimers (alpha(2)), utilizing a unique intermolecular redox-active disulfide center for the reduct...


    pub_type: 杂志文章


    authors: Wood ZA,Poole LB,Hantgan RR,Karplus PA

    更新日期:2002-04-30 00:00:00

  • Biosynthesis of prolyl hydroxylase: evidence for two separate dolichol-media pathways of glycosylation.

    abstract::Prolyl hydroxylase is a glycoprotein containing two nonidentical subunits, alpha and beta. The alpha subunit of prolyl hydroxylase isolated from 13-day-old chick embryos contains a single high mannose oligosaccharide having seven mannosyl residues. Two forms of alpha subunit have been shown to exist in enzyme purified...


    pub_type: 杂志文章


    authors: Kedersha NL,Tkacz JS,Berg RA

    更新日期:1985-10-08 00:00:00

  • Antisense L/D-oligodeoxynucleotide chimeras: nuclease stability, base-pairing properties, and activity at directing ribonuclease H.

    abstract::Ultraviolet thermal denaturation studies substantiate our earlier hypothesis that substitution of a L-nucleotide residue for a D-nucleotide within a DNA duplex permits a stable structure in which all bases are paired through Watson-Crick hydrogen bonds (Damha, M. J., Giannaris, P. A., Marfey, P., & Reid, L. S. (1991) ...


    pub_type: 杂志文章


    authors: Damha MJ,Giannaris PA,Marfey P

    更新日期:1994-06-28 00:00:00