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Biochemistry: Anastassis (Tassos) Perrakis

Anastassis Perrakis.jpg

Anastassis (Tassos) Perrakis, Ph.D. professorGroup leader

About Anastassis (Tassos) Perrakis

Research interest: Macromolecular Structures

Macromolecular structures are critical for understanding the function of proteins and their complexes and to evaluate and develop new drugs. A key methodology for understanding the structure of macromolecules is X-ray crystallography. My group is interested both in analysing macromolecular structures relevant for cancer, but also in developing the tools needed to decipher these structures.

I have been involved in many methodology oriented initiatives, providing scientific developments that enable specific software tools in determining macromolecular structures better and faster.

  • The development of the ARP/wARP suite for crystallographic model building has been the focus of my team for well over a decade. With more than 5,000 academic of users, close to one hundred active commercial licenses with companies in the biotechnology and pharmaceutical area, and well over 5,000 citations in international literature, ARP/wARP is established as a major tool for routine crystallographic structure determination. Our interest and major contributions to ARP/wARP have been to develop algorithms for docking the structure fragments to know sequences, building the side chain conformations, modeling surface loops, and developing the control systems and interfaces that make ARP/wARP easy and powerful to use for every crystallographer, novice or experienced.
  • Over the last few years, my team has been the basis for the development of the PDB_REDO suite. Capitalizing on our experience in developing algorithms for model building in ARP/wARP, we developed new tools that help rebuild and re-refine models that are already in the PDB or are about to be submitted to the PDB. PDB_REDO strives to help crystallographers submit better models to the public PDB archive, but also retro-actively re-refines and re-build the models available, to make sure they all benefit from the most recent developments in the theory and the software in macromolecular crystallography. As part of this effort we make available the for optimizing "working models" before they are submitted to the PDB.
    PDB_REDO has started a decade ago in the group of Gert Vriend at the Radboud University Medical Center at Nijmegen, as a software pipeline to remediate all PDB entries, by re-refining them with modern software. Since 2009, the original PDB_REDO developer Robbie Joosten has joined my team, and capitalising on our experience in developing algorithms for model building in ARP/wARP. We have since then developed new tools to rebuild macromolecular models and new decision and validation algorithms to improve and extend the score of this pipeline. PDB_REDO strives to help crystallographers submit better models to the public PDB archive, but also retro-actively re-refines and re-builds the models available, to make sure they all benefit from the most recent developments in the theory and the software in macromolecular crystallography. As part of this effort we make available the for optimizing "working models" before they are submitted to the PDB.
  • To determine macromolecular structures, it is important to first make the protein of interest using recombinant DNA technologies. A crucial step is in choosing the right "boundaries" of the protein to make, and many trials are typically required. To that end, in collaboration with the NKI Protein facility we have developed a suite of cloning vectors for ligation independent cloning and the Protein CCD software to design cloning experiments for protein expression in bacteria, insect or mammalian cells.

Our scientific interests revolve around a handful of specific research questions, that concern the interplay between function and structure. Most proteins have a specific enzymatic activity that drives a chemical reaction necessary to fulfill their physiological function. Many proteins, are made by multiple domains, or interact with other proteins, to direct their enzymatic activity in space and time. A common theme in our group is to understand the spatiotemporal control that interactions with other proteins (and with small domains within the same protein) exert on the activity of the 'host' protein, at the level of the molecular structure and physiological function. We use X-ray crystallography, X-ray scattering, and a variety of biophysical methods to answer these questions.

  • Autotaxin is a secreted phosphodiesterase that produces the signaling molecule lysophosphatidic acid, LPA. We have determined the structure of Autotaxin alone and with an in-house developed inhibitor, and have explained its catalytic mechanism. Future research lines focus on deciphering the role of Autotaxin isoforms, its mode of regulation, and the role of cell-surface interactions in its activity.
  • JBP1 is the protein that bind the unusual base J in parasites, and is homologous to the TET proteins involved in myeloid leukemia. We are focusing to understand how JBP1 acts to amplify base J in specific regions in the genome of parasites, and understanding the structure of the thymidine hydroxylation function, which is homologous between JBPs and TET proteins.
  • Geminin and its homologues Idas and GemC1 are coiled coil proteins involved in DNA replication licensing, making sure that exactly only one copy of the DNA is made during that massively parallel process . We try to understand how complexes between these proteins affect the function of Geminin in proliferation - differentiation decisions in cells, especially in modulating the interaction with Cdt1, a master regulation of replication licensing.
  • Mitotic kinases like Plk1-3, Mps1, BubR1 and Bub1, regulate the mitotic check point in various ways, making sure that only one copy of each chromatid goes in each daughter cell after cell division (mitosis). We are most interested to how the regulatory domains of these kinases, PDB and TPR domains, spatiotemporally regulated the various functions of these proteins, facilitating interactions with other proteins in the cell and regulating the activity of the kinase domains.


Adamopoulos, Nassos

Nassos Adamopoulos

Ph.D. student


I am interested in the role of lysophosphatidic acid (LPA) in tumor progression, angiogenesis and metastasis. Former structural studies in the group, have established the role of Autotaxin in LPA production and signaling. Recently, two new membrane proteins, members of the Glycerophosphodiester phosphodiesterase (GDE) family, which can produce LPA intracellularly were identified. Using structural biology tools, I am trying to understand the molecular mechanism of GDEs and characterise that new LPA generation pathway.



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Bart van Beusekom

Ph.D. student


After graduating in chemistry from the Radboud University Nijmegen, I am now working as a PhD student on the development of methods for protein structure determination in the PDB_REDO project.

With my supervisor Robbie Joosten, I will develop automated procedures to validate and transfer structural knowledge between evolutionary related protein structure models. Such developments will allow us to focus on detecting 'unusual' features that are important factors of a protein's structure and function.

My work will provide more informative and more reliable structure models, because all available structural knowledge is used simultaneously in a systematic manner.

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Damaskos, George

George Damaskos



I'm an adaptable and enthusiastic Computer Scientist specialized in Life Sciences Applications.
I think that knowledge transfer and interplay between different fields is feasible and leads the way for future breakthroughs.
I work under the Instruct-Ultra European project (, aiming to facilitate interconnection between different structural biology facilities in Europe, in terms of data exchange and integration.
Also, I spent some of my time maintaining and adding new features to CCD, the Crystallization Construct Designer (, a web application we have developed under the West-Life European project (
For me it is important to enjoy my job and stay focused to it.


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Tatjana Heidebrecht



After a three year training as a research assistant at the University of Bielefeld, I took a new challenge in the laboratory of A. Perrakis, to work on the JBP1 project. The JBP1 protein binds to DNA that contains the unusual DNA base J, that is essential for survival in many protozoan pathogens. In the last years I crystallized the DNA-binding domain of JBP1 and I characterized it extensively by biophysical methods. A remaining challenge is to determine the structure of full-length JBP1 and understand its relationship with the human TET enzymes that are involved in myeloid leukemia.

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Yoshitaka Hiruma

Postdoctoral Fellow


I performed my PhD research at Leiden University, where I studied the mechanism and interactions of cytochrome P450cam with paramagnetic NMR and X-ray crystallography. At the NKI, I will use biochemical, biophysical and structural approaches to study the function of the Mps1 and BubR1 (pseudo)kinases in mitosis, in collaboration with the group of Geert Kops group in the University Medical Center in Utrecht.

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Krista Joosten

Postdoctoral Fellow


After a PhD in theory of quantum properties in laser physics, I opted for research with a more direct link to socially relevant applications and specifically cancer research.  In the group of Anastassis Perrakis I use computer programming and modeling to improve building 3D protein models and study how to validate the quality of these models. We presently focus on combining experimental data, namely the three dimensional electron density maps that are computed from X-ray diffraction experiments of macromolecular crystals, knowledge from chemistry, and the statistical properties derived from existing models, to provide better structural models to scientists worldwide.

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Robbie Joosten

Research associate


The PDB_REDO project ( focuses on creating fully automated computational methods for optimizing, crystallographic structure models of proteins and nucleic acids. These methods can be applied while determining the structure of a new protein the lab, but also retro-actively to all known structure models in the Protein Data Bank. Taking full advantage of novel computational methods we provide to active crystallographers, but also to the diverse PDB user community crystallographic models with less errors and inaccuracies, helping to enhance the biological insight gained from such models in, for example, inhibitor design.

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Salgado Polo, Fernando

Fernando Salgado Polo

Ph.D. student


I studied Biochemistry at the Complutense University of Madrid and completed my master's degree at the VU University Amsterdam. My work in Tassos Perrakis's lab focuses on two main projects:

- Characterizing the catalysis and allosteric modulation of the lysophospholipase Autotaxin (ATX), the main producer of the bioactive lipid lysophosphatidic  acid (LPA), as well as the mechanism by which ATX presents its product to the LPA receptors at the cell surface.

- Understanding the intracellular trafficking and ligand specificity of several members in the glycerophosphodiester phosphodiesterase (GDE) family, namely, GDE2 and GDE3, which recognize GPI-anchored proteins.

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Ud Din Ahmad, Misbha

Misbha Ud Din Ahmad

Postdoctoral Fellow


I have completed my PhD in protein crystallography from the University of Konstanz. During my PhD I worked on archaeal transcriptional factors and used crystallography as a tool to understand the structural basis for their DNA binding. Here at NKI, in collaboration with the group of Geert Kops at Hubrecht Institute, I work on kinetochore associated proteins. Specifically, I aim to understand the factors that regulate dynein localization at the kinetochores. I use crystallography and biophysics to understand these mechanisms.

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Wienk, Hans

Hans Wienk

EU Grant Support


After receiving my PhD in Membrane Biochemistry at Utrecht University, I was trained in applied protein NMR at the Goethe University in Frankfurt am Main. Upon returning to Utrecht, after some years I became facility manager, responsible for solution machine usage of the (inter)national high-field NMR facility. Over the years I supported many local, national and international researchers with biomolecular NMR analyses and protein structure calculations.

For few years I combine NMR facility management with overall project management for the EU-funded structural biology project iNEXT. Currently, my interest increasingly focuses on the preparation and execution of European and national grants.

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Research updates View All Updates

  • Veni grant for Yoshitaka Hiruma

    Yoshitaka Hiruma, postdoc in the group of Anastassis Perrakis, will receive a Veni grant from the Netherlands Organisation for Scientific Research (Dutch abbreviation: NWO). He will use the grant of 250.000 Euro to further study the role of the Mps1 protein during cell division.

    Errors during cell division can cause all kinds of problems, including cancer. The division process consists of a number of separate phases. Between these phases there exist several checkpoints, molecular mechanisms that the cell uses to check whether it is safe to progress to the next phase. One such checkpoint is between the metaphase and anaphase. During the metaphase, the chromosomes are lined up and connected to the spindle apparatus. It is very important that all chromosomes are properly connected to the spindle microtubules, so that they will be neatly pulled apart and divided over the two daughter cells. Recently, Hiruma was the first author of a Science paper in which he and his colleagues describe how cells use the Mps1 protein to check whether all chromosomes are properly connected.

    The majority of solid tumors contain cells with an aberrant number of chromosomes, pointing to problems in the process described above. Hiruma now wants to study the Mps1 protein on the level of specific molecular and atomic interactions . Understanding the structures of the transient complexes that Mps1 makes during cell division,  could hopefully lead to the development of inhibitors of Mps1 interactions, that might in the future be developed as new anti-cancer drugs.

  • European Union invests 10 million Euro in research on the structure and function of complex proteins

    Aim of this initiative called iNEXT, is to determine new structures and functions of proteins and their complexes, by giving researchers integrated access to structural biology technologies such as NMR, electron microscopy and X-ray technologies. The project contributes to European goals for health and green economy, as fundamental knowledge of biological processes is important, for example, for
    the development of novel drugs and safe and sustainable food production methods.

    Groundbreaking research

    iNEXT will provide access to the most advanced facilities for structural biology in Europe. The collaborating facilities include advanced X-ray synchrotron sources in Grenoble, Hamburg, Oxford, Lund and Paris, high-field NMR facilities in Utrecht, Frankfurt, Florence, Brno, Lyon and Grenoble, imaging facilities in Oxford, Brno, Heidelberg, Leiden and Madrid and advanced biophysical characterization in Amsterdam. Together, these facilities will make it possible for European scientists to perform ground breaking protein research with technologies to which they otherwise would not have had access.

    Starting September 2015

    iNEXT ( is coordinated from the Netherlands by prof. Rolf Boelens (Utrecht University) with dr. Anastassis Perrakis (Netherlands Cancer Institute) as deputy coordinator. The program is
    setup in coordination with the European ESFRI projects Instruct, ESS, EU-OPENSCREEN and Euro-BioImaging. Researchers across Europe will be able to apply for access to the advanced facilities of iNEXT through a peer-review process. Starting September 1, 2015, the facilities will be available and
    proposals for access can be submitted.

Key publications View All Publications

  • Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling

    (2016) Nat Commun. Apr 14;7:11248

    Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A.

    Link to PubMed
  • CELL DIVISION CYCLE. Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling

    (2015) Science. Jun 12;348

    Hiruma Y, Sacristan C, Pachis ST, Adamopoulos A, Kuijt T2, Ubbink M, von Castelmur E Perrakis A, Kops GJ.

    Link to PubMed

Recent publications View All Publications

  • Building and rebuilding N-glycans in protein structure models

    (2019) Acta Crystallogr D Struct Biol. Apr 1;75(Pt 4):416-425.

    van Beusekom B, Wezel N, Hekkelman ML, Perrakis A, Emsley P, Joosten RP.

    Link to PubMed
  • Interactions between N-terminal Modules in MPS1 Enable Spindle Checkpoint Silencing

    (2019) Cell Rep. Feb 19;26(8):2101-2112.e6.

    Pachis ST, Hiruma Y, Tromer EC, Perrakis A, Kops GJPL.

    Link to PubMed


  • Office manager

    Mirna Ekelschot - van Diermen

  • E-mail

  • Telephone Number

    +31 20 512 9127


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