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- Al-Karadaghi, Salam, et al.
(författare)
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Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis
- 1997
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Ingår i: Structure. - 0969-2126. ; 5:11, s. 1501-1510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The metallation of closed ring tetrapyrroles resulting in the formation of hemes, chlorophylls and vitamin B12 is catalyzed by specific enzymes called chelatases. Ferrochelatase catalyzes the terminal step in heme biosynthesis by inserting ferrous ion into protoporphyrin IX by a mechanism that is poorly understood. Mutations in the human gene for ferrochelatase can result in the disease erythropoietic protoporphyria, and a further understanding of the mechanism of this enzyme is therefore of clinical interest. No three-dimensional structure of a tetrapyrrole metallation enzyme has been available until now. RESULTS: The three-dimensional structure of Bacillus subtilis ferrochelatase has been determined at 1.9 A resolution by the method of multiple isomorphous replacement. The structural model contains 308 of the 310 amino acid residues of the protein and 198 solvent molecules. The polypeptide is folded into two similar domains each with a four-stranded parallel beta sheet flanked by alpha helices. Structural elements from both domains build up a cleft, which contains several amino acid residues that are invariant in ferrochelatases from different organisms. In crystals soaked with gold and cadmium salt solutions, the metal ion was found to be coordinated to the conserved residue His 183, which is located in the cleft. This histidine residue has previously been suggested to be involved in ferrous ion binding. CONCLUSIONS: Ferrochelatase seems to have a structurally conserved core region that is common to the enzyme from bacteria, plants and mammals. We propose that porphyrin binds in the identified cleft; this cleft also includes the metal-binding site of the enzyme. It is likely that the structure of the cleft region will have different conformations upon substrate binding and release.
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| 2. |
- Lindkvist, Karin, et al.
(författare)
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Crystal structure of a SEA variant in complex with MHC class II reveals the ability of SEA to crosslink MHC molecules
- 2002
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Ingår i: Structure. - 0969-2126. ; 10:12, s. 1619-1626
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Tidskriftsartikel (refereegranskat)abstract
- Although the biological properties of staphylococcal enterotoxin A (SEA) have been well characterized, structural insights into the interaction between SEA and major histocompatibilty complex (MHC) class II have only been obtained by modeling. Here, the crystal structure of the D227A variant of SEA in complex with human MHC class II has been determined by X-ray crystallography. SEA(D227A) exclusively binds with its N-terminal domain to the alpha chain of HLA-DR1. The ability of one SEA molecule to crosslink two MHC molecules was modeled. It shows that this SEA molecule cannot interact with the T cell receptor (TCR) while a second SEA molecule interacts with MHC. Because of its relatively low toxicity, the D227A variant of SEA is used in tumor therapy.
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| 3. |
- Nevskaya, Natasha, et al.
(författare)
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Archaeal ribosomal protein L1: the structure provides new insights into RNA binding of the L1 protein family
- 2000
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Ingår i: Structure. - 0969-2126. ; 8:4, s. 363-371
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Tidskriftsartikel (refereegranskat)abstract
- Background: L1 is an important primary rRNA-binding protein, as well as a translational repressor that binds mRNA. It was shown that L1 proteins from some bacteria and archaea are functionally interchangeable within the ribosome and in the repression of translation. The crystal structure of bacterial L1 from Thermus thermophilus (TthL1) has previously been determined. Results: We report here the first structure of a ribosomal protein from archaea, L1 from Methanococcus jannaschii (MjaL1). The overall shape of the two-domain molecule differs dramatically from that of its bacterial counterpart (TthL1) because of the different relative orientations of the domains. Two strictly conserved regions of the amino acid sequence, each belonging to one of the domains and positioned close to each other in the interdomain cavity of TthL1, are separated by about 25 Å in MjaL1 owing to a significant opening of the structure. These regions are structurally highly conserved and are proposed to be the specific RNA-binding sites. Conclusions: The unusually high RNA-binding affinity of MjaL1 might be explained by the exposure of its highly conserved regions. The open conformation of MjaL1 is strongly stabilized by nonconserved interdomain interactions and suggests that the closed conformations of L1 (as in TthL1) open upon RNA binding. Comparison of the two L1 protein structures reveals a high conformational variability of this ribosomal protein. Determination of the MjaL1 structure offers an additional variant for fitting the L1 protein into electron-density maps of the 50S ribosomal subunit.
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| 7. |
- Hallberg, B. M., et al.
(författare)
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A new scaffold for binding haem in the cytochrome domain of the extracellular flavocytochrome cellobiose dehydrogenase
- 2000
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Ingår i: Structure. - 0969-2126 .- 1878-4186. ; 8:1, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: The fungal oxidoreductase cellobiose dehydrogenase (CDH) degrades both lignin and cellulose, and is the only known extracellular flavocytochrome. This haemoflavoenzyme has a multidomain organisation with a b-type cytochrome domain linked to a large flavodehydrogenase domain. The two domains can be separated proteolytically to yield a functional cytochrome and a flavodehydrogenase. Here, we report the crystal structure of the cytochrome domain of CDH. Results: The crystal structure of the b-type cytochrome domain of CDH from the wood-degrading fungus Phanerochaete chrysosporium has been determined at 1.9 Angstrom resolution using multiple isomorphous replacement ncluding anomalous scattering information. Three models of the cytochrome have been refined: the in vitro prepared cytochrome in its redox-inactive state (pH 7.5) and redox-active state (pH 4.6), as well as the naturally occurring cytochrome fragment. Conclusions: The 190-residue long cytochrome domain of CDH folds as a beta sandwich with the topology of the antibody Fab V-H domain. The haem iron is ligated by Met65 and His 163, which confirms previous results from spectroscopic studies. This is only the second example of a b-type cytochrome with this ligation, the first being cytochrome b(562). The haem-propionate groups are surface exposed and, therefore, might play a role in the association between the cytochrome and flavoprotein domain, and in interdomain electron transfer. There are no large differences in overall structure of the cytochrome at redoxactive pH as compared with the inactive form, which excludes the possibility that pH-dependent redox inactivation results from partial denaturation. From the electron-density map of the naturally occurring cytochrome, we conclude that it corresponds to the proteolytically prepared cytochrome domain.
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| 8. |
- Hendrickson, WA, et al.
(författare)
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New look and new outlook
- 2002
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Ingår i: STRUCTURE. - 0969-2126. ; 10:1, s. 1-1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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