title: Atomic resolution crystal structure of glutaredoxin 1 from Plasmodium falciparum and comparison with other glutaredoxins.
abstract: Glutaredoxins (Grxs) are redox proteins that use glutathione ((γ)Glu-Cys-Gly; GSH) as a cofactor. Plasmodium falciparum has one classic dithiol (CXXC) glutaredoxin (glutaredoxin 1; PfGrx1) and three monothiol (CXXS) Grx-like proteins (GLPs), which have five residue insertions prior to the active-site Cys. Here, the crystal structure of PfGrx1 has been determined by the sulfur single-wavelength anomalous diffraction (S-SAD) method utilizing intrinsic protein and solvent S atoms. Several residues were modelled with alternate conformations, and an alternate position was refined for the active-site Cys29 owing to radiation damage. The GSH-binding site is occupied by water polygons and buffer molecules. Structural comparison of PfGrx1 with other Grxs and Grx-like proteins revealed that the GSH-binding motifs (CXXC/CXXS, TVP, CDD, Lys26 and Gln/Arg63) are structurally conserved. Both the monothiol and dithiol Grxs possess three conserved water molecules; two of these were located in the GSH-binding site. PfGrx1 has several polar and charged amino-acid substitutions that provide structurally important additional hydrogen bonds and salt bridges missing in other Grxs.
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Road, New Delhi 110 067, India.
authors.forename: Manickam
authors.initials: M
authors.lastname: Yogavel
authors.affiliation: Department of Biochemistry, North-Eastern Hill University, Shillong 792 022, India.
authors.forename: Timir
authors.initials: T
authors.lastname: Tripathi
authors.affiliation: Department of Biochemistry, North-Eastern Hill University, Shillong 792 022, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Road, New Delhi 110 067, India.
authors.forename: Mudassir Meraj
authors.initials: MM
authors.lastname: Banday
authors.affiliation: Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University Giessen, 35392 Giessen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rahlfs
authors.affiliation: Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University Giessen, 35392 Giessen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Becker
authors.affiliation: European Molecular Biology Laboratory, 6 Rue Jules Horowitz, BP 181, 38042 Grenoble, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Belrhali
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Road, New Delhi 110 067, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D054477:Glutaredoxins / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D054477:Glutaredoxins; D013438:Sulfhydryl Compounds; D005978:Glutathione
keywords: S-SAD; dithiol; glutaredoxin; glutathione