High-resolution structures of a chitinase complexed with natural product cyclopentapeptide inhibitors: mimicry of carbohydrate substrate.

Abstract:

:Over the past years, family 18 chitinases have been validated as potential targets for the design of drugs against human pathogens that contain or interact with chitin during their normal life cycles. Thus far, only one potent chitinase inhibitor has been described in detail, the pseudotrisaccharide allosamidin. Recently, however, two potent natural-product cyclopentapeptide chitinase inhibitors, argifin and argadin, were reported. Here, we describe high-resolution crystal structures that reveal the details of the interactions of these cyclopeptides with a family 18 chitinase. The structures are examples of complexes of a carbohydrate-processing enzyme with high-affinity peptide-based inhibitors and show in detail how the peptide backbone and side chains mimic the interactions of the enzyme with chitooligosaccharides. Together with enzymological characterization, the structures explain why argadin shows an order of magnitude stronger inhibition than allosamidin, whereas argifin shows weaker inhibition. The peptides bind to the chitinase in remarkably different ways, which may explain the differences in inhibition constants. The two complexes provide a basis for structure-based design of potent chitinase inhibitors, accessible by standard peptide chemistry.

authors

Houston DR,Shiomi K,Arai N,Omura S,Peter MG,Turberg A,Synstad B,Eijsink VG,van Aalten DM

doi

10.1073/pnas.132060599

keywords:

subject

Has Abstract

pub_date

2002-07-09 00:00:00

pages

9127-32

issue

14

eissn

0027-8424

issn

1091-6490

pii

132060599

journal_volume

99

pub_type

杂志文章
  • Role for the Wilms tumor gene in genital development?

    abstract::Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here we describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.14.5383

    authors: van Heyningen V,Bickmore WA,Seawright A,Fletcher JM,Maule J,Fekete G,Gessler M,Bruns GA,Huerre-Jeanpierre C,Junien C

    更新日期:1990-07-01 00:00:00

  • Binding of histones H1 and H5 and their globular domains to four-way junction DNA.

    abstract::We have compared chicken erythrocyte linker histones H1 and H5 binding to a synthetic four-way DNA junction. Each histone binds to form a single complex, with an affinity which permits competition against a large excess of linear duplex DNA. The affinity of H5 is higher than that of H1. The globular domain from either...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.9.3525

    authors: Varga-Weisz P,Zlatanova J,Leuba SH,Schroth GP,van Holde K

    更新日期:1994-04-26 00:00:00

  • Affinity maturation of antibodies assisted by in silico modeling.

    abstract::Rational engineering methods can be applied with reasonable success to optimize physicochemical characteristics of proteins, in particular, antibodies. Here, we describe a combined CDR3 walking randomization and rational design-based approach to enhance the affinity of the human anti-gastrin TA4 scFv. The application ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0801221105

    authors: Barderas R,Desmet J,Timmerman P,Meloen R,Casal JI

    更新日期:2008-07-01 00:00:00

  • Asymmetric cryo-EM structure of the canonical Allolevivirus Qβ reveals a single maturation protein and the genomic ssRNA in situ.

    abstract::Single-stranded (ss) RNA viruses infect all domains of life. To date, for most ssRNA virions, only the structures of the capsids and their associated protein components have been resolved to high resolution. Qβ, an ssRNA phage specific for the conjugative F-pilus, has a T = 3 icosahedral lattice of coat proteins assem...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1609482113

    authors: Gorzelnik KV,Cui Z,Reed CA,Jakana J,Young R,Zhang J

    更新日期:2016-10-11 00:00:00

  • Mechanism of action of cholera toxin and the mobile receptor theory of hormone receptor-adenylate cyclase interactions.

    abstract::Rat liver membrane adenylate cyclase (EC 4.6.1.1) that has been stimulated more than 10-fold by cholera toxin (choleragen) has a 3-fold greater sensitivity to stimulation by glucagon. Choleragen similarly increases the sensitivity of cyclase to other peptide (ACTH, vasoactive intestinal polypeptide) and nonpeptide (ca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.1.33

    authors: Bennett V,O'Keefe E,Cuatrecasaş P

    更新日期:1975-01-01 00:00:00

  • Inherent noise can facilitate coherence in collective swarm motion.

    abstract::Among the most striking aspects of the movement of many animal groups are their sudden coherent changes in direction. Recent observations of locusts and starlings have shown that this directional switching is an intrinsic property of their motion. Similar direction switches are seen in self-propelled particle and othe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0811195106

    authors: Yates CA,Erban R,Escudero C,Couzin ID,Buhl J,Kevrekidis IG,Maini PK,Sumpter DJ

    更新日期:2009-04-07 00:00:00

  • Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban.

    abstract::The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism. Using solid-sta...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1303006110

    authors: Gustavsson M,Verardi R,Mullen DG,Mote KR,Traaseth NJ,Gopinath T,Veglia G

    更新日期:2013-10-22 00:00:00

  • Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility.

    abstract::An unusual cAMP signaling system mediates many of the events that prepare spermatozoa to meet the egg. Its components include the atypical, bicarbonate-stimulated, sperm adenylyl cyclase and a cAMP-dependent protein kinase (PKA) with the unique catalytic subunit termed Calpha(2) or C(s). We generated mice that lack Ca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0405580101

    authors: Nolan MA,Babcock DF,Wennemuth G,Brown W,Burton KA,McKnight GS

    更新日期:2004-09-14 00:00:00

  • Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells.

    abstract::Arsenic has played a key medicinal role against a variety of ailments for several millennia, but during the past century its prominence has been displaced by modern therapeutics. Recently, attention has been drawn to arsenic by its dramatic clinical efficacy against acute promyelocytic leukemia. Although toxic reactiv...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0306687101

    authors: Chou WC,Jie C,Kenedy AA,Jones RJ,Trush MA,Dang CV

    更新日期:2004-03-30 00:00:00

  • Structure and function of yeast Atg20, a sorting nexin that facilitates autophagy induction.

    abstract::The Atg20 and Snx4/Atg24 proteins have been identified in a screen for mutants defective in a type of selective macroautophagy/autophagy. Both proteins are connected to the Atg1 kinase complex, which is involved in autophagy initiation, and bind phosphatidylinositol-3-phosphate. Atg20 and Snx4 contain putative BAR dom...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1708367114

    authors: Popelka H,Damasio A,Hinshaw JE,Klionsky DJ,Ragusa MJ

    更新日期:2017-11-21 00:00:00

  • Tuning and switching a DNA polymerase motor with mechanical tension.

    abstract::Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced "tuning" and "switching." The internal conformational states of the enzyme motor are represented as nodes, and the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1033134100

    authors: Goel A,Astumian RD,Herschbach D

    更新日期:2003-08-19 00:00:00

  • Comparative genomics of the nonlegume Parasponia reveals insights into evolution of nitrogen-fixing rhizobium symbioses.

    abstract::Nodules harboring nitrogen-fixing rhizobia are a well-known trait of legumes, but nodules also occur in other plant lineages, with rhizobia or the actinomycete Frankia as microsymbiont. It is generally assumed that nodulation evolved independently multiple times. However, molecular-genetic support for this hypothesis ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1721395115

    authors: van Velzen R,Holmer R,Bu F,Rutten L,van Zeijl A,Liu W,Santuari L,Cao Q,Sharma T,Shen D,Roswanjaya Y,Wardhani TAK,Kalhor MS,Jansen J,van den Hoogen J,Güngör B,Hartog M,Hontelez J,Verver J,Yang WC,Schijlen E,Repin

    更新日期:2018-05-15 00:00:00

  • Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc.

    abstract::We have previously identified by cDNA cloning 5 mRNAs that appear in resting BALB/c 3T3 cells soon after growth stimulation by serum or platelet-derived growth factor. Five additional mRNAs of this class are described in this report. The mRNAs reached peak levels between 40 and 120 min after serum addition and rapidly...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.5.1182

    authors: Lau LF,Nathans D

    更新日期:1987-03-01 00:00:00

  • Complete amino acid sequence and homologies of human erythrocyte membrane protein band 4.2.

    abstract::The complete amino acid sequence for human erythrocyte band 4.2 has been derived from the nucleotide sequence of a full-length 2.35-kilobase (kb) cDNA. The 2.35-kb cDNA was isolated from a human reticulocyte cDNA library made in the expression vector lambda gt11. Of the 2348 base pairs (bp), 2073 bp encode 691 amino a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.2.613

    authors: Korsgren C,Lawler J,Lambert S,Speicher D,Cohen CM

    更新日期:1990-01-01 00:00:00

  • Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.

    abstract::High-resolution single nucleotide polymorphism genomic microarray (SNP-chip) is a useful tool to define gene dosage levels over the whole genome, allowing precise detection of deletions and duplications/amplifications of chromosomes in cancer cells. We found that this new technology can also identify breakpoints of ch...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0711039105

    authors: Kawamata N,Ogawa S,Zimmermann M,Niebuhr B,Stocking C,Sanada M,Hemminki K,Yamatomo G,Nannya Y,Koehler R,Flohr T,Miller CW,Harbott J,Ludwig WD,Stanulla M,Schrappe M,Bartram CR,Koeffler HP

    更新日期:2008-08-19 00:00:00

  • Human cone photoreceptor dependence on RPE65 isomerase.

    abstract::The visual (retinoid) cycle, the enzymatic pathway that regenerates chromophore after light absorption, is located primarily in the retinal pigment epithelium (RPE) and is essential for rod photoreceptor survival. Whether this pathway also is essential for cone photoreceptor survival is unknown, and there are no data ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0706367104

    authors: Jacobson SG,Aleman TS,Cideciyan AV,Heon E,Golczak M,Beltran WA,Sumaroka A,Schwartz SB,Roman AJ,Windsor EA,Wilson JM,Aguirre GD,Stone EM,Palczewski K

    更新日期:2007-09-18 00:00:00

  • Cross-peak-specific two-dimensional electronic spectroscopy.

    abstract::Intermolecular electronic coupling dictates the optical properties of molecular aggregate systems. Of particular interest are photosynthetic pigment-protein complexes that absorb sunlight then efficiently direct energy toward the photosynthetic reaction center. Two-dimensional (2D) ultrafast spectroscopy has been used...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0701201104

    authors: Read EL,Engel GS,Calhoun TR,Mancal T,Ahn TK,Blankenship RE,Fleming GR

    更新日期:2007-09-04 00:00:00

  • Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins.

    abstract::The energy landscape theory provides a general framework for describing protein folding reactions. Because a large number of studies, however, have focused on two-state proteins with single well-defined folding pathways and without detectable intermediates, the extent to which free energy landscapes are shaped up by t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0804774105

    authors: Calosci N,Chi CN,Richter B,Camilloni C,Engström A,Eklund L,Travaglini-Allocatelli C,Gianni S,Vendruscolo M,Jemth P

    更新日期:2008-12-09 00:00:00

  • The callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis.

    abstract::The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602844103

    authors: Takeda H,Caiment F,Smit M,Hiard S,Tordoir X,Cockett N,Georges M,Charlier C

    更新日期:2006-05-23 00:00:00

  • Copper control of bacterial nitrous oxide emission and its impact on vitamin B12-dependent metabolism.

    abstract::Global agricultural emissions of the greenhouse gas nitrous oxide (N2O) have increased by around 20% over the last 100 y, but regulation of these emissions and their impact on bacterial cellular metabolism are poorly understood. Denitrifying bacteria convert nitrate in soils to inert di-nitrogen gas (N2) via N2O and t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1314529110

    authors: Sullivan MJ,Gates AJ,Appia-Ayme C,Rowley G,Richardson DJ

    更新日期:2013-12-03 00:00:00

  • A superior descriptor of random textures and its predictive capacity.

    abstract::Two-phase random textures abound in a host of contexts, including porous and composite media, ecological structures, biological media, and astrophysical structures. Questions surrounding the spatial structure of such textures continue to pose many theoretical challenges. For example, can two-point correlation function...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905919106

    authors: Jiao Y,Stillinger FH,Torquato S

    更新日期:2009-10-20 00:00:00

  • Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopus development.

    abstract::Bone morphogenetic protein 4 (BMP-4) induces ventral mesoderm but represses dorsal mesoderm formation in Xenopus embryos. We show that BMP-4 inhibits two signaling pathways regulating dorsal mesoderm formation, the induction of dorsal mesoderm (Spemann organizer) and the dorsalization of ventral mesoderm. Ectopic expr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.26.12141

    authors: Re'em-Kalma Y,Lamb T,Frank D

    更新日期:1995-12-19 00:00:00

  • Induced transparency by interference or polarization.

    abstract::Polarization of optical fields is a crucial degree of freedom in the all-optical analogue of electromagnetically induced transparency (EIT). However, the physical origins of EIT and polarization-induced phenomena have not been well distinguished, which can lead to confusion in associated applications such as slow ligh...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2012982118

    authors: Wang C,Jiang X,Sweeney WR,Hsu CW,Liu Y,Zhao G,Peng B,Zhang M,Jiang L,Stone AD,Yang L

    更新日期:2021-01-19 00:00:00

  • Alpha-catenin is essential in intestinal adenoma formation.

    abstract::A loss-of-function mutation in the APC gene initiates colorectal carcinogenesis. Although the molecular mechanism of tumor initiation is complex, several modifier genes have been identified using mouse models, including the ApcMin mouse. Among the familial adenomatous polyposis mouse lines carrying a truncation mutati...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0705730104

    authors: Shibata H,Takano H,Ito M,Shioya H,Hirota M,Matsumoto H,Kakudo Y,Ishioka C,Akiyama T,Kanegae Y,Saito I,Noda T

    更新日期:2007-11-13 00:00:00

  • TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis.

    abstract::Dendrite morphogenesis is regulated by neuronal activity or neurotrophins, which may function by activating intrinsic signaling proteins, including Rho family GTPases. Here we report that activity- and brain-derived neurotrophic factor (BDNF)-dependent dendritic morphogenesis requires activation of geranylgeranyltrans...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0800846105

    authors: Zhou XP,Wu KY,Liang B,Fu XQ,Luo ZG

    更新日期:2008-11-04 00:00:00

  • The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling.

    abstract::The NOVH protein belongs to the emerging CCN [Connective tissue growth factor (CTGF), Cyr61/Cef10, nephroblastoma overexpressed gene] family of growth regulators sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Two members of the family (CYR61 and CTGF) are posit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.3.869

    authors: Perbal B,Martinerie C,Sainson R,Werner M,He B,Roizman B

    更新日期:1999-02-02 00:00:00

  • Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects.

    abstract::Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case-control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases include...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1105209108

    authors: Ren A,Qiu X,Jin L,Ma J,Li Z,Zhang L,Zhu H,Finnell RH,Zhu T

    更新日期:2011-08-02 00:00:00

  • Monkeys recognize the faces of group mates in photographs.

    abstract::Nonhuman primates possess a highly developed capacity for face recognition, which resembles the human capacity both cognitively and neurologically. Face recognition is typically tested by having subjects compare facial images, whereas there has been virtually no attention to how they connect these images to reality. C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0912174106

    authors: Pokorny JJ,de Waal FB

    更新日期:2009-12-22 00:00:00

  • Structural organization of a filamentous influenza A virus.

    abstract::Influenza is a lipid-enveloped, pleomorphic virus. We combine electron cryotomography and analysis of images of frozen-hydrated virions to determine the structural organization of filamentous influenza A virus. Influenza A/Udorn/72 virions are capsule-shaped or filamentous particles of highly uniform diameter. We show...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1002123107

    authors: Calder LJ,Wasilewski S,Berriman JA,Rosenthal PB

    更新日期:2010-06-08 00:00:00

  • Size limits of self-assembled colloidal structures made using specific interactions.

    abstract::We establish size limitations for assembling structures of controlled size and shape out of colloidal particles with short-ranged interactions. Through simulations we show that structures with highly variable shapes made out of dozens of particles can form with high yield, as long as each particle in the structure bin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1411765111

    authors: Zeravcic Z,Manoharan VN,Brenner MP

    更新日期:2014-11-11 00:00:00