Search results

1

3D Domain swapping, protein oligomerization, and amyloid formation.

100%

Jaskólski M.

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2001

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vol. 48

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issue 4

807-827

EN

In 3D domain swapping, first described by Eisenberg, a structural element of a monomeric protein is replaced by the same element from another subunit. This process requires partial unfolding of the closed monomers that is then followed by adhesion and reconstruction of the original fold but from elements contributed by different subunits. If the interactions are reciprocal, a closed-ended dimer will be formed, but the same phenomenon has been suggested as a mechanism for the formation of open-ended polymers as well, such as those believed to exist in amyloid fibrils. There has been a rapid progress in the study of 3D domain swapping. Oligomers higher than dimers have been found, the monomer-dimer equilibrium could be controlled by mutations in the hinge element of the chain, a single protein has been shown to form more than one domain-swapped structure, and recently, the possibility of simultaneous exchange of two structural domains by a single molecule has been demonstrated. This last discovery has an important bearing on the possibility that 3D domain swapping might be indeed an amyloidogenic mechanism. Along the same lines is the discovery that a protein of proven amyloidogenic properties, human cystatin C, is capable of 3D domain swapping that leads to oligomerization. The structure of do-main-swapped human cystatin C dimers explains why a naturally occurring mutant of this protein has a much higher propensity for aggregation, and also suggests how this same mechanism of 3D domain swapping could lead to an open-ended polymer that would be consistent with the cross-β structure, which is believed to be at the heart of the molecular architecture of amyloid fibrils.

2

Sequence analysis of enzymes with asparaginase activity.

64%

Borek D., Jaskólski M.

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2001

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vol. 48

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issue 4

893-902

EN

Asparaginases catalyze the hydrolysis of asparagine to aspartic acid and ammonia. Enzymes with asparaginase activity play an important role both in the metabolism of all living organisms as well as in pharmacology. The main goal of this paper is to attempt a classification of all known enzymes with asparaginase activity, based on their amino acid sequences. Some possible phylogenetic consequences are also discussed using dendrograms and structural information derived from crystallographic studies.

3

Why a "benign" mutation kills enzyme activity. Structure-based analysis of the A176V mutant of Saccharomyces cerevisiae L-asparaginase I

64%

Bonthron D. T., Jaskólski M.

Acta Biochimica Polonica

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1997

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vol. 44

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issue 3

491-504

4

Crystallization and preliminary crystallographic studies of a new crystal form of papain from Cariea papaya

51%

Kozak M., Kozian E., Grzonka Z., Jaskólski M.

Acta Biochimica Polonica

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1997

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vol. 44

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issue 3

601-605

5

Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase.

51%

Kozak M., Jaskólski M., Röhm K. H.

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2000

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vol. 47

|

issue 3

807-814

EN

Periplasmic Escherichia coli L-asparaginase II with Y25F mutation in the active-site cavity has been obtained by recombinant techniques. The protein was crystallized in a new hexagonal form (P6522). Single crystals of this polymorph, suitable for X-ray diffraction, were obtained by vapor diffusion using 2-methyl-2,4-pentanediol as precipitant (pH 4.8). The crystals are characterized by a = 81.0, c = 341.1 Å and diffract to 2.45 Å resolution. The asymmetric unit contains two protein molecules arranged into an AB dimer. The physiologically relevant ABA'B' homotetramer is generated by the action of the crystallographic 2-fold axis along [1, -1, 0]. Kinetic studies show that the loss of the phenolic hydroxyl group at position 25 brought about by the replacement of Y with F strongly impairs kcat without significantly affecting Km.

6

Sequence determination and analysis of S-adenosyl-L-homocysteine hydrolase from yellow lupine (Lupinus luteus).

51%

Brzeziński K., Janowski R., Podkowiński J., Jaskólski M.

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EN

The coding sequences of two S-adenosyl-L-homocysteine hydrolases (SAHases) were identified in yellow lupine by screenig of a cDNA library. One of them, corresponding to the complete protein, was sequenced and compared with 52 other SAHase sequences. Phylogenetic analysis of these proteins identified three groups of the enzymes. Group A comprises only bacterial sequences. Group B is subdivided into two subgroups, one of which (B1) is formed by animal sequences. Subgroup B2 consist of two distinct clusters, B2a and B2b. Cluster B2b comprises all known plant sequences, including the yellow lupine enzyme, which are distinguished by a 50-residue insert. Group C is heterogeneous and contains SAHases from Archaea as well as a new class of animal enzymes, distinctly different from those in group B1.

7

Molecular recognition motifs in cytidinium and 2'-deoxycytidinium salts with composite anions

51%

Gilski M., Jaskólski M.

Acta Biochimica Polonica

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1998

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vol. 45

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issue 4

917-928

8

Structure-function relationship of serine protease-protein inhibitor interaction.

33%

Otlewski J., Jaskólski M., Buczek O., Cierpicki T., Czapińska H., Krowarsch D., Smalas A. O., Stachowiak D., Szpineta A., Dadlez M.

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2001

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vol. 48

|

issue 2

419-428

EN

We report our progress in understanding the structure-function relationship of the interaction between protein inhibitors and several serine proteases. Recently, we have determined high resolution solution structures of two inhibitors Apis mellifera chymotrypsin inhibitor-1 (AMCI-I) and Linum usitatissimum trypsin inhibitor (LUTI) in the free state and an ultra high resolution X-ray structure of BPTI. All three inhibitors, despite totally different scaffolds, contain a solvent exposed loop of similar conformation which is highly complementary to the enzyme active site. Isothermal calorimetry data show that the interaction between wild type BPTI and chymotrypsin is entropy driven and that the enthalpy component opposes complex formation. Our research is focused on extensive mutagenesis of the four positions from the protease binding loop of BPTI: P1, P1', P3, and P4. We mutated these residues to different amino acids and the variants were characterized by determination of the association constants, stability parameters and crystal structures of protease-inhibitor complexes. Accommodation of the P1 residue in the S1 pocket of four proteases: chymotrypsin, trypsin, neutrophil elastase and cathepsin G was probed with 18 P1 variants. High resolution X-ray structures of ten complexes between bovine trypsin and P1 variants of BPTI have been determined and compared with the cognate P1 Lys side chain. Mutations of the wild type Ala16 (P1') to larger side chains always caused a drop of the association constant. According to the crystal structure of the Leu16 BPTI-trypsin complex, introduction of the larger residue at the P1' position leads to steric conflicts in the vicinity of the mutation. Finally, mutations at the P4 site allowed an improvement of the association with several serine proteases involved in blood clotting. Conversely, introduction of Ser, Val, and Phe in place of Gly12 (P4) had invariably a destabilizing effect on the complex with these proteases.

9

Structural studies of cysteine proteases and their inhibitors.

27%

Grzonka Z., Jankowska E., Kasprzykowski F., Kasprzykowska R., Łankiewicz L., Wiczk W., Wieczerzak E., Ciarkowski J., Drabik P., Janowski R., Kozak M., Jaskólski M., Grubb A.

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2001

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vol. 48

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issue 1

1-20

EN

Cysteine proteases (CPs) are responsible for many biochemical processes occurring in living organisms and they have been implicated in the development and progression of several diseases that involve abnormal protein turnover. The activity of CPs is regulated among others by their specific inhibitors: cystatins. The main aim of this review is to discuss the structure-activity relationships of cysteine proteases and cystatins, as well as of some synthetic inhibitors of cysteine proteases structurally based on the binding fragments of cystatins.

Refine search results

3D Domain swapping, protein oligomerization, and amyloid formation.

Sequence analysis of enzymes with asparaginase activity.

Why a "benign" mutation kills enzyme activity. Structure-based analysis of the A176V mutant of Saccharomyces cerevisiae L-asparaginase I

Crystallization and preliminary crystallographic studies of a new crystal form of papain from Cariea papaya

Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase.

Sequence determination and analysis of S-adenosyl-L-homocysteine hydrolase from yellow lupine (Lupinus luteus).

Molecular recognition motifs in cytidinium and 2'-deoxycytidinium salts with composite anions

Structure-function relationship of serine protease-protein inhibitor interaction.

Structural studies of cysteine proteases and their inhibitors.