Crystal structure of conserved protein PH1136 from Pyrococcus horikoshii.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
Min Yao
Publications and source records attributed to Min Yao.
In regard to Lee et al. Intensity-modulated radiation therapy for head-and-neck cancer: the UCSF experience focusing on target volume delineation. (Int J Radiat Oncol Biol Phys 2003;57:49-60).
Explore the source record for details and available documents.
Head and Neck Neoplasms↗
Crystal structure of human p120 homologue protein PH1374 from Pyrococcus horikoshii.
Explore the source record for details and available documents.
Bacterial Proteins↗
The N- and C-terminal peptides of hIL8/CXCL8 are ligands for hCXCR1 and hCXCR2.
Chemokines are small cytokines that function in immune responses, wound healing, and pathological conditions such as chronic inflammation and tumorigenesis. This multifunctionality has been attributed primarily to ligand interaction with multiple or dimerized receptors. However, multifunctionality could also result from interactions of the receptors with small peptides produced by processing of the chemokines. Chemokine peptides are functional in vivo, but it is not yet known whether they can interact with and activate their receptors. The work presented here examines the interactions between the two forms of human interleukin 8 (hIL-8), and its N- and C-peptides, with the chemokine receptors hCXCR1 and hCXCR2. We used a Tet-on retroviral system to introduce CXCR1 into mouse NIH 3T3 cells (that lack endogenous CXCR1) and monitored activation of this receptor by the ligands by using quantitative Ca2+ imaging and mitogen-activated protein kinase (MAPK) activation. We found that the N and C termini of the chemokine can stimulate the respective CXCR1 to induce intracellular Ca2+ release and MAPK activation independent of the other regions of the molecules. Furthermore, we showed that these peptides can also stimulate chemotaxis of several cell types, including primary human microvascular endothelial cells, and that this function is specific and mediated by hCXCR1 and/or hCXCR2. These findings advance understanding of the multifunctionality exhibited by chemokines, reveal a new mode of functional regulation, and may serve as the basis for therapeutic targeting.
Animals↗
Structural implications for heavy metal-induced reversible assembly and aggregation of a protein: the case of Pyrococcus horikoshii CutA.
CutA is a small protein that appears to be involved in the mechanism of divalent metal cation tolerance in microorganisms. Here we report the crystal structure of Pyrococcus horikoshii CutA (PhoCutA), with and without Cu(2+), and its metal-binding properties. Crystallographic analyses revealed that PhoCutA forms a stable trimeric structure with intertwined antiparallel beta-strands. The crystal structure of the Cu(2+)-PhoCutA complex shows that the Cu(2+) is located at a trimer-trimer interface and is recognized by the side chains of one Asp(48) from each trimer. In an in vitro experiment, PhoCutA bound to several heavy metals, most of which led to reversible aggregation of the protein; i.e. the aggregates could be completely solubilized by addition of ethylenediamine tetraacetic acid (EDTA) or dialysis against metal free buffer. Substitution of Asp(48) with Ala led to a decrease in the amount of aggregates, suggesting the significant contribution of Asp(48) to the reversible aggregation. To the best of our knowledge, this is the first report which provides the structural evidence for heavy metal-induced multimerization of a protein.
Amino Acid Sequence↗
Flash-cooling of macromolecular crystals in a capillary to overcome increased mosaicity.
This paper describes the usefulness of flash-cooling in a capillary (FCC) for X-ray diffraction data collection from macromolecular crystals. FCC may be applied when conventional cooling using a cryoloop fails. This technique cools crystals in a capillary instead of in a cryoloop and thus cools crystals more slowly than conventional cooling. Measurements of cooling rates have shown that the time taken to reach the final temperature is two to eight times longer using FCC than using a cryoloop, depending on the volume of cryoprotectant solution around the crystal. Using this cooling technique, the crystal structures of isocitrate dehydrogenase and protein L-isoaspartate O-methyltransferase have been solved at 1.95 and at 2.50 A resolution, respectively. Both crystals could not be cooled by the conventional method using a cryoloop. Moreover, diffraction data from crystals of the hypothetical proteins PH-A and PH-B were also collected successfully using the FCC method. These results show that some crystals, especially larger ones, need to be cooled slowly.
Crystallography, X-Ray↗
The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process.
Mitochondrial cytochrome c oxidase plays an essential role in aerobic cellular respiration, reducing dioxygen to water in a process coupled with the pumping of protons across the mitochondrial inner membrane. An aspartate residue, Asp-51, located near the enzyme surface, undergoes a redox-coupled x-ray structural change, which is suggestive of a role for this residue in redox-driven proton pumping. However, functional or mechanistic evidence for the involvement of this residue in proton pumping has not yet been obtained. We report that the Asp-51 --> Asn mutation of the bovine enzyme abolishes its proton-pumping function without impairment of the dioxygen reduction activity. Improved x-ray structures (at 1.8/1.9-A resolution in the fully oxidized/reduced states) show that the net positive charge created upon oxidation of the low-spin heme of the enzyme drives the active proton transport from the interior of the mitochondria to Asp-51 across the enzyme via a water channel and a hydrogen-bond network, located in tandem, and that the enzyme reduction induces proton ejection from the aspartate to the mitochondrial exterior. A peptide bond in the hydrogen-bond network critically inhibits reverse proton transfer through the network. A redox-coupled change in the capacity of the water channel, induced by the hydroxyfarnesylethyl group of the low-spin heme, suggests that the channel functions as an effective proton-collecting region. Infrared results indicate that the conformation of Asp-51 is controlled only by the oxidation state of the low-spin heme. These results indicate that the low-spin heme drives the proton-pumping process.
Animals↗
Reaction intermediate structures of 1-aminocyclopropane-1-carboxylate deaminase: insight into PLP-dependent cyclopropane ring-opening reaction.
The pyridoxal 5'-phosphate-dependent enzymes have been evolved to catalyze diverse substrates and to cause the reaction to vary. 1-Aminocyclopropane-1-carboxylate deaminase catalyzes the cyclopropane ring-opening reaction followed by deamination specifically. Since it was discovered in 1978, the enzyme has been widely investigated from the mechanistic and physiological viewpoints because the substrate is a precursor of the plant hormone ethylene and the enzymatic reaction includes a cyclopropane ring-opening. We have previously reported the crystal structure of the native enzyme. Here we report the crystal structures of the two reaction intermediates created by the mutagenesis complexed with the substrate. The substrate was validated in the active site of two forms: 1). covalent-bonded external aldimine with the coenzyme in the K51T form and 2). the non-covalent interaction around the coenzyme in the Y295F form. The orientations of the substrate in both structures were quite different form each other. In concert with other site-specific mutation experiments, this experiment revealed the ingenious and unique strategies that are used to achieve the specific activity. The substrate incorporated into the active site is reactivated by a two-phenol charge relay system to lead to the formation of a Schiff base with the coenzyme. The catalytic Lys51 residue may play a novel role to abstract the methylene proton from the substrate in cooperation with other factors, the carboxylate group of the substrate and the electron-adjusting apparatuses of the coenzyme.
Binding Sites↗
Construction of an EGF receptor-mediated histone H1(0)-based gene delivery system.
PURPOSE: To construct an EGF receptor (EGF-R)-mediated histone H1(0)-based gene delivery system for gene therapy. METHODS: A recombinant DNA containing histone H1(0), EGF-R ligand, and endosomalytic domains was constructed in a prokaryotic vector and expressed in E. coli. Expression of the beta-galactosidase (beta-gal) gene in the tumor cells and tissues was observed after transduction of the beta-gal gene packaged by purified fusion proteins in vitro and in vivo. RESULTS: As an extension of the research on previously reported chemically synthetic composite polypeptide gene delivery systems, this genetically engineered polypeptide has proved to be capable of targeting the beta-galactosidase (beta-gal) gene into EGF-R-positive cancer cells both in vitro and in vivo. We also studied the time course of beta-gal gene expression in tumor tissues delivered in vivo by this polypeptide vector. At 24 h after administration, expression of the beta-galactosidase gene in tumor reached peak levels. The dosage optimization of administered polyplex was also investigated. The optimal dose of polyplex per mouse was 1 microg DNA packaged by 3 microg of composite polypeptide. CONCLUSIONS: The genetically engineered polypeptide based on histone H1(0) is a promising gene delivery system targeting EGF-R.
Animals↗
Crystal structure of the monomeric isocitrate dehydrogenase in the presence of NADP+: insight into the cofactor recognition, catalysis, and evolution.
NADP+-dependent monomeric isocitrate dehydrogenase (IDH) from the nitrogen-fixing bacterium Azotobacter vinelandii (AvIDH) is one of members of the beta-decarboxylating dehydrogenase family and catalyzes the dehydration and decarboxylation of isocitrate to yield 2-oxoglutrate and CO2 in the Krebs cycle. We solved the crystal structure of the AvIDH in complex with cofactor NADP+ (AvIDH-NADP+ complex). The final refined model shows the closed form that has never been detected in any previously solved structures of beta-decarboxylating dehydrogenases. The structure also reveals all of the residues that interact with NADP+. The structure-based sequence alignment reveals that these residues were not conserved in any other dimeric NADP+-dependent IDHs. Therefore the NADP+ specificity of the monomeric and dimeric IDHs was independently acquired through the evolutional process. The AvIDH was known to show an exceptionally high turnover rate. The structure of the AvIDH-NADP+ complex indicates that one loop, which is not present in the Escherichia coli IDHs, reliably stabilizes the conformation of the nicotinamide mononucleotide of the bound NADP+ by forming a few hydrogen bonds, and such interactions are considered to be important for the monomeric enzyme to initiate the hydride transfer reaction immediately. Finally, the structure of the AvIDH is compared with that of other dimeric NADP-IDHs. Several structural features demonstrate that the monomeric IDHs are structurally more related to the eukaryotic dimeric IDHs than to the bacterial dimeric IDHs.
Amino Acid Sequence↗
A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts.
NF-kappa B-induced gene expression contributes significantly to the pathogenesis of inflammatory diseases such as arthritis. I kappa B kinase (IKK) is the converging point for the activation of NF-kappa B by a broad spectrum of inflammatory agonists and is thus a novel target for therapeutic intervention. We describe a small molecule, selective inhibitor of IKK-2, SC-514, which does not inhibit other IKK isoforms or other serine-threonine and tyrosine kinases. SC-514 inhibits the native IKK complex or recombinant human IKK-1/IKK-2 heterodimer and IKK-2 homodimer similarly. IKK-2 inhibition by SC-514 is selective, reversible, and competitive with ATP. SC-514 inhibits transcription of NF-kappa B-dependent genes in IL-1 beta-induced rheumatoid arthritis-derived synovial fibroblasts in a dose-dependent manner. When the mechanism of NF-kappa B activation was evaluated in the presence of this inhibitor, several interesting observations were found. First, SC-514 did not inhibit the phosphorylation and activation of the IKK complex. Second, there was a delay but not a complete blockade in I kappa B alpha phosphorylation and degradation; likewise there was a slightly slowed, decreased import of p65 into the nucleus and a faster export of p65 from the nucleus. Finally, both I kappa B alpha and p65 were comparable substrates for IKK-2, with similar Km and Kcat values, and SC-514 inhibited the phosphorylation of either substrate similarly. Thus, the effect of SC-514 on cytokine gene expression may be a combination of inhibiting I kappa B alpha phosphorylation/degradation, affecting NF-kappa B nuclear import/export as well as the phosphorylation and transactivation of p65.
Active Transport, Cell Nucleus↗
Crystal structure of the ectodomain of human FcalphaRI.
Human FcalphaRI (CD89) is the receptor specific for IgA, an immunoglobulin that is abundant in mucosa and is also found in high concentrations in serum. Although FcalphaRI is an immunoglobulin Fc receptor (FcR), it differs in many ways from FcRs for other immunoglobulin classes. The genes of most FcRs are located on chromosome 1 at 1q21-23, whereas FcalphaRI is on chromosome 19, at 19q13.4, a region called the leukocyte receptor complex, because it is clustered with several leukocyte receptor families including killer cell inhibitory receptors (KIRs) and leukocyte Ig-like receptors (LIRs). The amino acid sequence of FcalphaRI shares only 20% homology with other FcRs but it has around 35% homology with its neighboring LIRs and KIRs. In this work, we analyzed the crystal structure of the ectodomain of FcalphaRI and examined structure similarities between FcalphaRI and KIR2DL1, KIR2DL2 and LIR-1. Our data show that FcalphaRI, KIRs, and LIRs share a common hydrophobic core in their interdomain interface, and FcalphaRI is evolutionally closer to LIR than KIR.
Amino Acid Sequence↗
Crystal structures of the ribonuclease MC1 mutants N71T and N71S in complex with 5'-GMP: structural basis for alterations in substrate specificity.
Ribonuclease MC1 (RNase MC1), isolated from bitter gourd seeds, is a uridine specific RNase belonging to the RNase T2 family. Mutations of Asn71 in RNase MC1 to the amino acids Thr (N71T) and Ser (N71S) in guanosine preferential RNases altered the substrate specificity from uridine specific to guanosine specific, as shown by the transphosphorylation of diribonucleoside monophosphates [Numata, T., et al. (2001) Biochemistry 40, 524-530]. To elucidate the structural basis for the alteration of substrate specificity, crystal structures of the RNase MC1 mutants N71T and N71S, free or complexed with 5'-GMP, were determined at resolutions higher than 2 A. In the N71T-5'-GMP and N71S-5'-GMP complexes, the guanine moiety was, as in the case of the uracil moiety bound to wild-type RNase MC1, firmly stabilized in the B2 site by an extensive network of hydrogen bonds and hydrophobic interactions. Structure comparisons showed that mutations of Asn71 to Thr or Ser cause an enlargement of the B2 site, which then make it feasible to insert a guanine base into the B2 site of mutants N71T and N71S. This binding further allows for hydrogen bonding interaction of the side chain hydroxyl groups of Thr71 or Ser71 with the N7 atom of the guanine base. The mode of guanine binding of mutants N71T and N71S was found to be essentially identical to that of a guanosine preferential RNase NW from Nicotiana glutinosa. In particular, hydrogen bonds between the N7 atom of the guanine base and the hydroxyl groups of the amino acids at position 71 (RNase MC1 numbering) were completely conserved in three guanosine preferential enzymes, thereby indicating that the hydrogen bond may play an essential role in guanine binding in guanosine preferential RNases in the RNase T2 family. Consequently, it can be concluded that amino acids at position 71 (RNase MC1 numbering) serve as one of the determinants for substrate specificity (or preference) in the RNase T2 fimily by changing the size and shape of the B2 site.
Crystallography, X-Ray↗
[Proliferation-inhibiting effect of advanced glycation end products modified human serum albumin to vascular endothelial cell ECV304].
OBJECTIVE: To study the proliferation-inhibiting and apoptosis-inducing effects of advanced glycation end products (AGE) modified human serum albumin (AGE-HSA) on human vein endothelial cells. METHODS: Human umbilical vein endothelial cells ECV304 were cultured in vitro with AGE-HSA of the concentrations of 12.5, 25, 50, 100, and 200 micro g/ml for 6, 12, 24, or 48 hour, then 20 micro l of 5 mg/ml MTT were added and the optical density (OD) at each time point was determined. Another ECV304 cells were cultured with AGE-HAS for 2, 4, or 8 days and then were stained with trypan blue to calculate the number of dead cells so as to calculate the proliferation-inhibiting rate. Another ECV304 cells were cultured with AGE-HAS for 6, 12, 24, or 48 hours and then stained with annexin V Fitc and propidium iodide (PI). Flow cytometry was used to calculate the annexin V Fitc positive cells (early and middle stage apoptotic cells) and Annexin V Fitc/PL positive cells (late apoptotic cells). Inverted microscope, transmission electron microscope, and fluorescence microscope were used to observe the histological changes of apoptotic cells. FCV304 cells incubated with HSA of the above-mentioned and without addition of the other agents concentrations were used as controls. RESULTS: The OD values of ECV304 cells cultured for 48 h with low concentrations (12.5, 25, and 50 micro g/ml) of AGE-HSA were not significantly different from those of the control (1.104 +/- 0.080, 1.098 +/- 0.097 and 1.059 +/- 0.122 VS. 1.159 +/- 0.088, all P > 0.05). The OD values of ECV304 cells cultured with low concentrations of AGE-HSA for 4 days and 6 days were significantly lower than those in the control group. The OD values of ECV304 cells cultured with high concentrations (100 and 200 micro g/ml) of AGE-HSA for 6 - 48 hours decreased to 0.117 +/- 0.033 and 0.081 +/- 0.020 in comparison with that of the control group (P < 0.01). Flow cytometry and fluorescence microscopy showed higher proportions of apoptotic cells among the ECV304 cells cultured with high concentrations of AGE-HAS than among the control cells at each time point (P < 0.01). The numbers of cells in the control group exponentially increased after culture for 2, 4, and 6 days. The number of cells cultured with low concentrations of AGE-HAS for 2 days was not significantly different from that of the control group (P > 0.05), however, the numbers of cells cultured with low concentrations of AGE-HAS for 4 and 6 days were significantly lower than those of the control group (both P < 0.01). The numbers of cells cultured with 100 or 200 micro g/ml AGE-HAS for 2 days were significantly lower than those of the control group (both P < 0.01) with a proliferation-inhibiting rate of 39.56% +/- 2.82% and 60.32% +/- 4.51% respectively. The apoptotic rates in cells cultured with low concentrations of AGE-HAS for 48 hours were not significantly different from those in the control group. The apoptotic rates in cells cultured with 100 or 200 micro g/ml AGE-HAS for 6, 12, 24, or 48 hours were significantly higher than those in the control group (all P < 0.01). The apoptotic rates in 200 micro g/ml group at different time points were significantly higher than those in the 100 micro g/ml group (P < 0.05 or 0.01). The apoptotic rate and number of apoptotic cells increased along with the increase of culture time and concentration of AGE-HAS. Microscopy showed morphological changes among the cells cultured with 100 micro g/ml AGE-HAS for 6, 12, 24, and 48 hours and the numbers of apoptotic cells, mainly late apoptotic cells, and dead cells increased remarkably since the cells were cultured for 48 hours. CONCLUSION: AGE-HSA inhibits the proliferation of vascular endothelial cells and induces apoptosis in dose and time dependent manner. AGE modification-induced pathobiological cascade may be involved in the pathogenesis of impaired wound healing in diabetes by the mechanism of angiogenesis retardation.
Apoptosis↗
Insight into a natural Diels-Alder reaction from the structure of macrophomate synthase.
The Diels-Alder reaction, which forms a six-membered ring from an alkene (dienophile) and a 1,3-diene, is synthetically very useful for construction of cyclic products with high regio- and stereoselectivity under mild conditions. It has been applied to the synthesis of complex pharmaceutical and biologically active compounds. Although evidence on natural Diels-Alderases has been accumulated in the biosynthesis of secondary metabolites, there has been no report on the structural details of the natural Diels-Alderases. The function and catalytic mechanism of the natural Diels-Alderase are of great interest owing to the diversity of molecular skeletons in natural Diels-Alder adducts. Here we present the 1.70 A resolution crystal structure of the natural Diels-Alderase, fungal macrophomate synthase (MPS), in complex with pyruvate. The active site of the enzyme is large and hydrophobic, contributing amino acid residues that can hydrogen-bond to the substrate 2-pyrone. These data provide information on the catalytic mechanism of MPS, and suggest that the reaction proceeds via a large-scale structural reorganization of the product.
Alcohols↗
Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice.
A large number of epidemiological studies have shown that regular use of aspirinor other nonsteroidal anti-inflammatory drugs (NSAIDs) results in a 40-50% reduced risk of colorectal cancer (CRC). Furthermore, NSAIDs cause the regression of preexisting adenomas in patients with familial adenomatous polyposis and significantly inhibit tumor growth in animal models of CRC. To establish a CRC liver metastasis model, we implanted mouse colon tumor MC-26 cells into the splenic subcapsule of BALB/c mice, after which mice were given either standard chow or chow containing the cyclooxygenase (COX)-2-specific inhibitor rofecoxib, alone or in combination with the standard antineoplastic agents, 5-fluoruracil or irinotecan. After 14 days, mice that were given rofecoxib or irinotecan, but not 5-fluoruracil, had significantly smaller primary tumors and fewer metastases. Rofecoxib, at clinical anti-inflammatory plasma concentrations, enhanced the effects of both antineoplastic agents when used in combination. Biochemical analyses of the primary splenic tumor in rofecoxib-treated mice showed no alteration in COX-1 expression, but significant decreases in the expression of the tumor-promoting proteins COX-2, cyclin D1, cytosolic beta-catenin, matrix metalloproteinases-2 and -9, and vascular endothelial cell- derived growth factor. Rofecoxib also decreased growth-enhancing prostaglandin E(2) and tumor-suppressive interleukin-10, whereas antineoplastic interleukin-12 was increased. Two separate survival studies were performed. When mice were fed chow containing 0.01% rofecoxib beginning on day 0 after tumor cell implantation, which achieved clinical anti-inflammatory plasma concentrations, survival time was significantly longer compared with mice given control chow. After 30 days, mortality in the control group was 90%, whereas only one mouse (5%) treated with rofecoxib had died after 30 days. In the second survival study, all of the mice were initially fed with regular chow after tumor cell implantation. On day 7, mice were randomly divided into three dietary groups: control chow, low-dose (0.01%) rofecoxib chow, and high-dose (0.025%) rofecoxib chow. After 28 days, mortality was 100%, 20%, and 10% in control, low-, and high-dose rofecoxib fed groups, respectively. These studies demonstrate that rofecoxib decreases the growth and metastatic potential of CRC in mice through multiple mechanisms. These studies in mice also provide important information that supports the benefit of COX-2 inhibition, not only in the prevention of CRC, but also potentially in the treatment of this common malignancy. Clinical trials will be necessary to assess the utility of COX-2 inhibitors as adjuvant therapy for early-stage disease and as potential agents, either alone or in combination, with more established drugs, for the treatment of refractory CRC.
Animals↗
[Complications in selective coronary angiography: analysis of 9196 cases].
OBJECTIVE: To study the incidence rates, risk factors, prevention and treatments of complications of selective coronary arteriography. METHODS: A retrospective survey was conducted on the data of the incidence and annual distribution characteristics of complications among 9 196 cases that underwent selective coronary arteriography performed October 1987 to December 2000, and analyze the risk factors and prevention and treatment of these complications. RESULTS: The total complication rate was 1.33%. The procedure-related mortality rates were 0.02%. The incidence rate of non-fatal Q wave myocardial infarction, coronary artery spasm, severe arrhythmia, severe contrast allergic reaction, peripheral vascular complication, and heart failure in coronary arteriography was 0.01%, 0.13%, 0.29%, 0.04%, 0.35%, and 0.08%, respectively. No emergent coronary artery bypass surgery was required in patients with coronary arteriography. The independent risk factors of the complications of coronary arteriography included unstable angina, coronary multivessel disease, left main coronary artery disease and heart failure. CONCLUSION: The complication rate of coronary arteriography decrease with the accumulation of experience. The complication rate in this group is lower than in other reports probably due to strictly selecting of indication and active prevention and treatment of complications.
Anaphylaxis↗
Crystal structure of hyperthermophilic archaeal initiation factor 5A: a homologue of eukaryotic initiation factor 5A (eIF-5A).
Eukaryotic initiation factor 5A (eIF-5A) is ubiquitous in eukaryotes and archaebacteria and is essential for cell proliferation and survival. The crystal structure of the eIF-5A homologue (PhoIF-5A) from a hyperthermophilic archaebacterium Pyrococcus horikoshii OT3 was determined at 2.0 A resolution by the molecular replacement method. PhoIF-5A is predominantly composed of beta-strands comprising two distinct folding domains, an N-domain (residues 1-69) and a C-domain (residues 72-138), connected by a short linker peptide (residues 70-71). The N-domain has an SH3-like barrel, while the C-domain folds in an (oligonucleotide/oligosaccharide binding) OB fold. Comparison of the structure of PhoIF-5A with those of archaeal homologues from Methanococcus jannaschii and Pyrobaculum aerophilum showed that the N-domains could be superimposed with root mean square deviation (rmsd) values of 0.679 and 0.624 A, while the C-domains gave higher values of 1.824 and 1.329 A, respectively. Several lines of evidence suggest that eIF-5A functions as a biomodular protein capable of interacting with protein and nucleic acid. The surface representation of electrostatic potential shows that PhoIF-5A has a concave surface with positively charged residues between the N- and C-domains. In addition, a flexible long hairpin loop, L1 (residues 33-41), with a hypusine modification site is positively charged, protruding from the N-domain. In contrast, the opposite side of the concave surface at the C-domain is mostly negatively charged. These findings led to the speculation that the concave surface and loop L1 at the N-domain may be involved in RNA binding, while the opposite side of the concave surface in the C-domain may be involved in protein interaction.
Amino Acid Sequence↗