ChemBioChem

Cover image for ChemBioChem

Special Issue: Protein Design

February 6, 2004

Volume 5, Issue 2

Pages 141–246

    1. Cover Picture: Consensus Design of Repeat Proteins (ChemBioChem 2/2004) (page 141)

      Patrik Forrer, H. Kaspar Binz, Michael T. Stumpp and Andreas Plückthun

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200490000

      The cover picture shows an illustration of consensus design, a powerful protein-engineering method that is based on sequence alignments of homologous proteins. An alignment of ankyrin repeats is shown in the sequence plane, and a consensus-designed ankyrin repeat protein based on this alignment is shown in ribbon representation hovering over the plane. See more about the consensus design of repeat proteins and its use in repeat-protein library construction in the article by Plückthun et al. on p. 183 ff. Such libraries promise to be excellent sources of a novel type of specific binding molecules. The help of Christian Zahnd in preparing this picture is gratefully acknowledged.

    2. You have free access to this content
      Editorial: Protein Design (pages 143–144)

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300843

    3. Lipase-Specific Foldases (pages 152–161)

      Frank Rosenau, Jan Tommassen and Karl-Erich Jaeger

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300761

      Thumbnail image of graphical abstract

      The meaning of Lif: Bacterial lipases represent a very important class of enzymes used in biotechnology. Many of them require a specific foldase, Lif, which is anchored to the bacterial inner membrane, as shown in the figure. Lifs act as chaperones providing essential steric information needed to fold lipases into their enzymatically active conformation.

    4. Functional Changes in the Family of Type 3 Copper Proteins During Evolution (pages 163–169)

      Elmar Jaenicke and Heinz Decker

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300714

      Thumbnail image of graphical abstract

      Blue blood, brown melanin: Two very different proteins share a type 3 copper active site. Tyrosinases catalyze the hydroxylation and oxidation of phenols, which results in the formation of the brown pigment melanin. Hemocyanins, on the other hand, are the oxygen-transport proteins in the hemolymph of truly blue-blooded animals such as spiders, scorpions, crabs, and octopus. Both proteins are closely related by evolution. But why is a hemocyanin not a tyrosinase and vice versa? What is the origin of cooperativity in these proteins? We review and discuss the structural and functional changes that took place in the evolution of type 3 copper proteins.

    5. Coiled Coil Domains: Stability, Specificity, and Biological Implications (pages 170–176)

      Jody M. Mason and Katja M. Arndt

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300781

      Thumbnail image of graphical abstract

      Twist and shout: Coiled-coil forming α-helices are of great significance in understanding tertiary structural formation (the figure shows GCN4; an example of a parallel dimeric coiled coil), the design of new proteins, and the control of the oligomeric state. The apparent simplicity of coiled coils is misleading, and rules governing such features are far from fully established. Requirements for the specific pairings of helices during coiled-coil formation are discussed, as are the peculiarities within such domains that give proteins their unique function. By taking advantage of our increasing understanding of this structural class, a growing number of biological and therapeutic applications are being sought.

    6. Combinatorial Approaches To Novel Proteins (pages 177–182)

      Tomoaki Matsuura, Andreas Ernst, David L. Zechel and Andreas Plückthun

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300755

      Thumbnail image of graphical abstract

      The Nature of the fold: The number of folds found in nature is most likely to be limited and therefore two fundamental questions arise: did nature realize all possible folds and can we select for novel folded proteins? Here we review experimental approaches to explore areas in protein-sequence space not sampled by nature.

    7. Consensus Design of Repeat Proteins (pages 183–189)

      Patrik Forrer, H. Kaspar Binz, Michael T. Stumpp and Andreas Plückthun

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300762

      Thumbnail image of graphical abstract

      Repeating yourself: Consensus design exploits statistical sequence information for protein engineering. Recently, consensus design was successfully adapted to repeat proteins, which are abundant binding molecules present in most forms of life. They feature consecutive copies of short homologous sequences, which form homologous structural units (repeats). Single repeats have been consensus designed and then assembled into elongated repeat domains. Such designed repeat domains not only give structural and biophysical insight into the repetitive architecture of these non-globular proteins, but libraries of such molecules have also proven to be good starting points for the generation of novel binding molecules with very favorable properties.

    8. Construction of an Artificial Receptor Protein (“Anticalin”) Based on the Human Apolipoprotein D (pages 191–199)

      Martin Vogt and Arne Skerra

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300703

      Thumbnail image of graphical abstract

      A human scaffold: Anticalins, a class of engineered proteins derived from the lipocalin structural family with antibody-like ligand-binding properties, can recognize not only haptens but also antigens. Human apolipoprotein D was recruited as a scaffold for the generation of an anticalin directed against hemoglobin (see figure). Our findings demonstrate that the characteristic region of four hypervariable loops that forms the ligand-binding site of the lipocalins can be considerably reshaped to bind even macromolecular targets.

    9. Addressing the Challenge of Changing the Specificity of RNase T1 with Rational and Evolutionary Approaches (pages 200–205)

      Marc Struhalla, Rico Czaja and Ulrich Hahn

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300715

      Thumbnail image of graphical abstract

      Being specific: Changing the specificity of ribonuclease T1 has been a challenge for the past 15 years, and several protein engineering methods with a special focus on shifting the guanine to an adenine specificity have been employed. Here we describe recent efforts to address this task with rational and evolutionary approaches aimed at the selection of new RNase T1 variants (the active site of one is shown here) with remarkable shifts in specificity.

    10. Chimeras of the Homing Endonuclease PI-SceI and the Homologous Candida tropicalis Intein: A Study to Explore the Possibility of Exchanging DNA-Binding Modules to Obtain Highly Specific Endonucleases with Altered Specificity (pages 206–213)

      Shawn Steuer, Vera Pingoud, Alfred Pingoud and Wolfgang Wende

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300718

      Thumbnail image of graphical abstract

      Homing in on genes: The design of highly specific endonucleases with new specificities for use in genome engineering is an extremely demanding task. We studied the intein homing endonuclease PI-SceI (see picture) and exchanged its DNA-binding modules with homologous elements from the Candida intein. The results demonstrate the potential of this enzyme family for the production of dedicated endonucleases.

    11. Learning from Directed Evolution: Theoretical Investigations into Cooperative Mutations in Lipase Enantioselectivity (pages 214–223)

      Marco Bocola, Nikolaj Otte, Karl-Erich Jaeger, Manfred T. Reetz and Walter Thiel

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300731

      Thumbnail image of graphical abstract

      Molecular dynamics simulations provide insight into the origin of enhanced enantioselectivity in lipase-catalyzed ester hydrolysis and explain remote and cooperative effects of mutations introduced by directed evolution (see diagram).

    12. Modulating Functional Loop Movements: The Role of Highly Conserved Residues in the Correlated Loop Motions (pages 224–230)

      Kannan Gunasekaran and Ruth Nussinov

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300732

      Thumbnail image of graphical abstract

      Moving with the times: The relationship between enzyme function and flexibility provides an opportunity to explore enzymatic activity through controling the flexibility of a functional loop. Molecular-dynamics simulations, and sequence and structural analyses of β-1,4-galactosyltransferase reveals that loops coupled in motions also have highly conserved residues involved in the loop–loop interactions (see figure).

    13. Adaptation of Class-13 α-Amylases to Diverse Living Conditions (pages 231–239)

      Anni Linden and Matthias Wilmanns

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200300734

      Thumbnail image of graphical abstract

      Factors influencing thermostability have been determined mainly by statistical analysis of protein structures, but no general rule that applies for proteins from different families could be established and the basis of thermal characteristics is still poorly understood. A closer look at structural features of family-13 α-amylases revealed the presence of superimposable di-/tri-metal centres in two monomeric hyperthermostable amylases, not present in less thermostable members of the same family.

    14. You have free access to this content
      Preview: ChemBioChem 2/2004 (page 246)

      Version of Record online: 29 JAN 2004 | DOI: 10.1002/cbic.200490002

SEARCH

SEARCH BY CITATION