ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Observation of covalent intermediates in an enzyme mechanism at atomic resolution (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-10-13
    Description: In classical enzymology, intermediates and transition states in a catalytic mechanism are usually inferred from a series of biochemical experiments. Here, we derive an enzyme mechanism from true atomic-resolution x-ray structures of reaction intermediates. Two ultra-high resolution structures of wild-type and mutant d-2-deoxyribose-5-phosphate (DRP) aldolase complexes with DRP at 1.05 and 1.10 angstroms unambiguously identify the postulated covalent carbinolamine and Schiff base intermediates in the aldolase mechanism. In combination with site-directed mutagenesis and (1)H nuclear magnetic resonance, we can now propose how the heretofore elusive C-2 proton abstraction step and the overall stereochemical course are accomplished. A proton relay system appears to activate a conserved active-site water that functions as the critical mediator for proton transfer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heine, A -- DeSantis, G -- Luz, J G -- Mitchell, M -- Wong, C H -- Wilson, I A -- GM44154/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 12;294(5541):369-74.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11598300" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde-Lyases/*chemistry/genetics/*metabolism ; Amino Acid Substitution ; Binding Sites ; Catalysis ; Chemistry, Physical ; Crystallization ; Crystallography, X-Ray ; Escherichia coli/enzymology ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Ligands ; Lysine/chemistry ; Models, Chemical ; Mutagenesis, Site-Directed ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Physicochemical Phenomena ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Protons ; Ribosemonophosphates/*chemistry/*metabolism ; Schiff Bases ; Water
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-04-16
    Description: A highly specific Diels-Alder protein catalyst was made by manipulating the antibody repertoire of the immune system. The catalytic antibody 13G5 catalyzes a disfavored exo Diels-Alder transformation in a reaction for which there is no natural enzyme counterpart and that yields a single regioisomer in high enantiomeric excess. The crystal structure of the antibody Fab in complex with a ferrocenyl inhibitor containing the essential haptenic core that elicited 13G5 was determined at 1.95 angstrom resolution. Three key antibody residues appear to be responsible for the observed catalysis and product control. Tyrosine-L36 acts as a Lewis acid activating the dienophile for nucleophilic attack, and asparagine-L91 and aspartic acid-H50 form hydrogen bonds to the carboxylate side chain that substitutes for the carbamate diene substrate. This hydrogen-bonding scheme leads to rate acceleration and also pronounced stereoselectivity. Docking experiments with the four possible ortho transition states of the reaction explain the specific exo effect and suggest that the (3R,4R)-exo stereoisomer is the preferred product.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heine, A -- Stura, E A -- Yli-Kauhaluoma, J T -- Gao, C -- Deng, Q -- Beno, B R -- Houk, K N -- Janda, K D -- Wilson, I A -- CA27489/CA/NCI NIH HHS/ -- GM-43858/GM/NIGMS NIH HHS/ -- P01 CA27489/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1934-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute of Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9506943" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Catalytic/*chemistry/immunology/metabolism ; Catalysis ; Chemistry, Organic ; Crystallography, X-Ray ; Ferrous Compounds/*chemistry/immunology/metabolism ; Haptens/chemistry/immunology ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Immunoglobulin Fab Fragments/chemistry ; Models, Molecular ; Organic Chemistry Phenomena ; Stereoisomerism ; Thermodynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Deeply inverted electron-hole recombination in a luminescent antibody-stilbene complex (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-03-01
    Description: The blue-emissive antibody EP2-19G2 that has been elicited against trans-stilbene has unprecedented ability to produce bright luminescence and has been used as a biosensor in various applications. We show that the prolonged luminescence is not stilbene fluorescence. Instead, the emissive species is a charge-transfer excited complex of an anionic stilbene and a cationic, parallel pi-stacked tryptophan. Upon charge recombination, this complex generates exceptionally bright blue light. Complex formation is enabled by a deeply penetrating ligand-binding pocket, which in turn results from a noncanonical interface between the two variable domains of the antibody.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Debler, Erik W -- Kaufmann, Gunnar F -- Meijler, Michael M -- Heine, Andreas -- Mee, Jenny M -- Pljevaljcic, Goran -- Di Bilio, Angel J -- Schultz, Peter G -- Millar, David P -- Janda, Kim D -- Wilson, Ian A -- Gray, Harry B -- Lerner, Richard A -- DK19038/DK/NIDDK NIH HHS/ -- GM38273/GM/NIGMS NIH HHS/ -- GM56528/GM/NIGMS NIH HHS/ -- R01 GM038273/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1232-5. doi: 10.1126/science.1153445.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18309081" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/*chemistry/genetics/immunology ; Antigen-Antibody Complex ; Binding Sites, Antibody ; Crystallization ; Crystallography, X-Ray ; *Electrons ; Fluorescence ; Fluorescence Polarization ; Haptens/chemistry/immunology ; Hydrophobic and Hydrophilic Interactions ; Immunoglobulin Variable Region/*chemistry/immunology ; Ligands ; Luminescence ; Mutation ; Oxidation-Reduction ; Protein Structure, Tertiary ; Spectrometry, Fluorescence ; Spectrum Analysis ; Stilbenes/*chemistry/immunology ; Tryptophan/chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Immune versus natural selection: antibody aldolases with enzymic rates but broader scope (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-02-12
    Description: Structural and mechanistic studies show that when the selection criteria of the immune system are changed, catalytic antibodies that have the efficiency of natural enzymes evolve, but the catalytic antibodies are much more accepting of a wide range of substrates. The catalytic antibodies were prepared by reactive immunization, a process whereby the selection criteria of the immune system are changed from simple binding to chemical reactivity. This process yielded aldolase catalytic antibodies that approximated the rate acceleration of the natural enzyme used in glycolysis. Unlike the natural enzyme, however, the antibody aldolases catalyzed a variety of aldol reactions and decarboxylations. The crystal structure of one of these antibodies identified the reactive lysine residue that was selected in the immunization process. This lysine is deeply buried in a hydrophobic pocket at the base of the binding site, thereby accounting for its perturbed pKa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barbas, C F 3rd -- Heine, A -- Zhong, G -- Hoffmann, T -- Gramatikova, S -- Bjornestedt, R -- List, B -- Anderson, J -- Stura, E A -- Wilson, I A -- Lerner, R A -- CA27489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Dec 19;278(5346):2085-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9405338" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Catalytic/chemistry/immunology/*metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Decarboxylation ; *Evolution, Molecular ; Fructose-Bisphosphate Aldolase/chemistry/immunology/*metabolism ; Glycolysis ; Hydrogen-Ion Concentration ; Immunization ; Immunoglobulin Fab Fragments/chemistry/immunology/*metabolism ; Kinetics ; Lysine/chemistry/metabolism ; Mice ; Models, Molecular ; Protein Conformation ; Pyridoxal/metabolism ; Selection, Genetic ; Substrate Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Vinylogous chain branching catalysed by a dedicated polyketide synthase module (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-09-21
    Description: Bacteria use modular polyketide synthases (PKSs) to assemble complex polyketides, many of which are leads for the development of clinical drugs, in particular anti-infectives and anti-tumoral agents. Because these multifarious compounds are notoriously difficult to synthesize, they are usually produced by microbial fermentation. During the past two decades, an impressive body of knowledge on modular PKSs has been gathered that not only provides detailed insight into the biosynthetic pathways but also allows the rational engineering of enzymatic processing lines to yield structural analogues. Notably, a hallmark of all PKS modules studied so far is the head-to-tail fusion of acyl and malonyl building blocks, which leads to linear backbones. Yet, structural diversity is limited by this uniform assembly mode. Here we demonstrate a new type of PKS module from the endofungal bacterium Burkholderia rhizoxinica that catalyses a Michael-type acetyl addition to generate a branch in the carbon chain. In vitro reconstitution of the entire PKS module, X-ray structures of a ketosynthase-branching didomain and mutagenesis experiments revealed a crucial role of the ketosynthase domain in branching the carbon chain. We present a trapped intermediary state in which acyl carrier protein and ketosynthase are covalently linked by the branched polyketide and suggest a new mechanism for chain alkylation, which is functionally distinct from terpenoid-like beta-branching. For the rice seedling blight toxin rhizoxin, one of the strongest known anti-mitotic agents, the non-canonical polyketide modification is indispensable for phytotoxic and anti-tumoral activities. We propose that the formation of related pharmacophoric groups follows the same general scheme and infer a unifying vinylogous branching reaction for PKS modules with a ketosynthase-branching-acyl-carrier-protein architecture. This study unveils the structure and function of a new PKS module that broadens the biosynthetic scope of polyketide biosynthesis and sets the stage for rationally creating structural diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bretschneider, Tom -- Heim, Joel B -- Heine, Daniel -- Winkler, Robert -- Busch, Benjamin -- Kusebauch, Bjorn -- Stehle, Thilo -- Zocher, Georg -- Hertweck, Christian -- England -- Nature. 2013 Oct 3;502(7469):124-8. doi: 10.1038/nature12588. Epub 2013 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena 07745, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24048471" target="_blank"〉PubMed〈/a〉
    Keywords: Burkholderia/chemistry/*enzymology/genetics ; Catalysis ; Crystallography, X-Ray ; Lactones/metabolism ; Macrolides/chemistry ; *Models, Molecular ; Mutagenesis ; Polyketide Synthases/genetics/*metabolism ; Protein Structure, Tertiary
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...