Brynda J

References (4)

Title : Structure-activity relationship and biochemical evaluation of novel fibroblast activation protein and prolyl endopeptidase inhibitors with alpha-ketoamide warheads - Simkova_2021_Eur.J.Med.Chem_224_113717
Author(s) : Simkova A , Ormsby T , Sidej N , Slavetinska LP , Brynda J , Beranova J , Sacha P , Majer P , Konvalinka J
Ref : Eur Journal of Medicinal Chemistry , 224 :113717 , 2021
Abstract : Peptidomimetic inhibitors of fibroblast activation protein (FAP) are regarded as promising tools for tumor targeting in vivo. Even though several peptidomimetic compounds with nanomolar potency have been described, broad chemical space for further modification remained unexplored. Therefore, we set to analyze the structure-activity relationship (SAR) of pseudopeptide compound series with alpha-ketoamide warheads in order to explore the contributions of the P1' and P2' moieties to the inhibitory potency. A series of novel inhibitors bearing varied P1' and/or P2' moieties was synthesized by combining a Passerini reaction-Amine Deprotection-Acyl Migration (PADAM) approach with peptide coupling and subsequent oxidation. The resulting compounds inhibited FAP and the related prolyl endopeptidase (PREP) with potencies in the nanomolar to sub-nanomolar range. The most potent FAP inhibitor IOCB22-AP446 (6d, IC(50) = 89 pM) had about 36-fold higher inhibition potency than the most potent inhibitor published to date. The compounds were selective over FAP's closest homolog DPP-IV, were stable in human and mouse plasma and in mouse microsomes, and displayed minimal cytotoxicity in tissue cultures.
ESTHER : Simkova_2021_Eur.J.Med.Chem_224_113717
PubMedSearch : Simkova_2021_Eur.J.Med.Chem_224_113717
PubMedID: 34371463

Title : Crystal structure of the cold-adapted haloalkane dehalogenase DpcA from Psychrobacter cryohalolentis K5 - Tratsiak_2019_Acta.Crystallogr.F.Struct.Biol.Commun_75_324
Author(s) : Tratsiak K , Prudnikova T , Drienovska I , Damborsky J , Brynda J , Pachl P , Kuty M , Chaloupkova R , Rezacova P , Kuta Smatanova I
Ref : Acta Crystallographica F Struct Biol Commun , 75 :324 , 2019
Abstract : Haloalkane dehalogenases (HLDs) convert halogenated aliphatic pollutants to less toxic compounds by a hydrolytic mechanism. Owing to their broad substrate specificity and high enantioselectivity, haloalkane dehalogenases can function as biosensors to detect toxic compounds in the environment or can be used for the production of optically pure compounds. Here, the structural analysis of the haloalkane dehalogenase DpcA isolated from the psychrophilic bacterium Psychrobacter cryohalolentis K5 is presented at the atomic resolution of 1.05 A. This enzyme exhibits a low temperature optimum, making it attractive for environmental applications such as biosensing at the subsurface environment, where the temperature typically does not exceed 25 degrees C. The structure revealed that DpcA possesses the shortest access tunnel and one of the most widely open main tunnels among structural homologs of the HLD-I subfamily. Comparative analysis revealed major differences in the region of the alpha4 helix of the cap domain, which is one of the key determinants of the anatomy of the tunnels. The crystal structure of DpcA will contribute to better understanding of the structure-function relationships of cold-adapted enzymes.
ESTHER : Tratsiak_2019_Acta.Crystallogr.F.Struct.Biol.Commun_75_324
PubMedSearch : Tratsiak_2019_Acta.Crystallogr.F.Struct.Biol.Commun_75_324
PubMedID: 31045561
Gene_locus related to this paper: psyck-q1qbb9

Title : Crystallization and preliminary X-ray diffraction analysis of the wild-type haloalkane dehalogenase DhaA and its variant DhaA13 complexed with different ligands - Stsiapanava_2011_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_67_253
Author(s) : Stsiapanava A , Chaloupkova R , Fortova A , Brynda J , Weiss MS , Damborsky J , Smatanova IK
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 67 :253 , 2011
Abstract : Haloalkane dehalogenases make up an important class of hydrolytic enzymes which catalyse the cleavage of carbon-halogen bonds in halogenated aliphatic compounds. There is growing interest in these enzymes owing to their potential use in environmental and industrial applications. The haloalkane dehalogenase DhaA from Rhodococcus rhodochrous NCIMB 13064 can slowly detoxify the industrial pollutant 1,2,3-trichloropropane (TCP). Structural analysis of this enzyme complexed with target ligands was conducted in order to obtain detailed information about the structural limitations of its catalytic properties. In this study, the crystallization and preliminary X-ray analysis of complexes of wild-type DhaA with 2-propanol and with TCP and of complexes of the catalytically inactive variant DhaA13 with the dye coumarin and with TCP are described. The crystals of wild-type DhaA were plate-shaped and belonged to the triclinic space group P1, while the variant DhaA13 can form prism-shaped crystals belonging to the orthorhombic space group P2(1)2(1)2(1) as well as plate-shaped crystals belonging to the triclinic space group P1. Diffraction data for crystals of wild-type DhaA grown from crystallization solutions with different concentrations of 2-propanol were collected to 1.70 and 1.26 A resolution, respectively. A prism-shaped crystal of DhaA13 complexed with TCP and a plate-shaped crystal of the same variant complexed with the dye coumarin diffracted X-rays to 1.60 and 1.33 A resolution, respectively. A crystal of wild-type DhaA and a plate-shaped crystal of DhaA13, both complexed with TCP, diffracted to atomic resolutions of 1.04 and 0.97 A, respectively.
ESTHER : Stsiapanava_2011_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_67_253
PubMedSearch : Stsiapanava_2011_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_67_253
PubMedID: 21301099
Gene_locus related to this paper: rhoso-halo1

Title : Crystallization and preliminary X-ray analysis of a novel haloalkane dehalogenase DbeA from Bradyrhizobium elkani USDA94 - Prudnikova_2009_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_65_353
Author(s) : Prudnikova T , Mozga T , Rezacova P , Chaloupkova R , Sato Y , Nagata Y , Brynda J , Kuty M , Damborsky J , Smatanova IK
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 65 :353 , 2009
Abstract : A novel enzyme, DbeA, belonging to the haloalkane dehalogenase family (EC 3.8.1.5) was isolated from Bradyrhizobium elkani USDA94. This haloalkane dehalogenase is closely related to the DbjA enzyme from B. japonicum USDA110 (71% sequence identity), but has different biochemical properties. DbeA is generally less active and has a higher specificity towards brominated and iodinated compounds than DbjA. In order to understand the altered activity and specificity of DbeA, its mutant variant DbeA1, which carries the unique fragment of DbjA, was also constructed. Both wild-type DbeA and DbeA1 were crystallized using the sitting-drop vapour-diffusion method. The crystals of DbeA belonged to the primitive orthorhombic space group P2(1)2(1)2(1), while the crystals of DbeA1 belonged to the monoclinic space group C2. Diffraction data were collected to 2.2 A resolution for both DbeA and DbeA1 crystals.
ESTHER : Prudnikova_2009_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_65_353
PubMedSearch : Prudnikova_2009_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_65_353
PubMedID: 19342778
Gene_locus related to this paper: brael-e2rv62