Endocrinological evaluation of dawn phenomenon in patients with diabetes and comparison of insulin glargine U-100 biosimilar (Insulin Glargine BS Injection "Lilly") and glargine U-300 (Lantus XR): a randomized controlled study.

We investigated the pathophysiology of the dawn phenomenon by examining the effects of changes in blood glucose levels from late night to early morning on various hormones in a group taking glargine BS and a group taking Lantus XR, with the goal of achieving better glycemic control. Patients with types 1 and 2 diabetes scheduled for inpatient education were divided into BS and XR groups. Blood glucose levels were tracked from 0:00 to 7:00, while blood samples were extracted at 3:00 and 7:00 to measure glucose levels and hormones related to the dawn phenomenon. Overall, we analyzed blood sample and intermittently scanned Continuous Glucose Monitoring data of 43 and 40 patients, respectively. From 0:00 to 7:00, the mean blood glucose was significantly lower in the BS group, although the fluctuation was similar (p < 0.0001). The BS group also exhibited significantly higher ∆ACTH (p = 0.0215) and ∆ cortisol (p = 0.0430) than the XR group. In the BS group, ∆Glu exhibited a significant negative correlation with ∆ACTH and ∆cortisol (p = 0.0491). Similar findings were not observed in the XR group. These results suggest that XR may be a better choice for long-acting insulin since it is less likely to induce cortisol secretion. Further, analysis of the dawn phenomenon and non-dawn phenomenon groups showed the mean CPR levels at 3:00 and 7:00 were significantly higher in the latter (p = 0.0135). This supports the conventional belief that appropriate basal insulin replacement therapy is a beneficial treatment for the dawn phenomenon.

Oncogenic mutations Q61L and Q61H confer active form-like structural features to the inactive state (state 1) conformation of H-Ras protein.

GTP-bound forms of Ras proteins (Ras•GTP) assume two interconverting conformations, "inactive" state 1 and "active" state 2. Our previous study on the crystal structure of the state 1 conformation of H-Ras in complex with guanosine 5'-(ß, γ-imido)triphosphate (GppNHp) indicated that state 1 is stabilized by intramolecular hydrogen-bonding interactions formed by Gln61. Since Ras are constitutively activated by substitution mutations of Gln61, here we determine crystal structures of the state 1 conformation of H-Ras•GppNHp carrying representative mutations Q61L and Q61H to observe the effect of the mutations. The results show that these mutations alter the mode of hydrogen-bonding interactions of the residue 61 with Switch II residues and induce conformational destabilization of the neighboring regions. In particular, Q61L mutation results in acquirement of state 2-like structural features. Moreover, the mutations are likely to impair an intramolecular structural communication between Switch I and Switch II. Molecular dynamics simulations starting from these structures support the above observations. These findings may give a new insight into the molecular mechanism underlying the aberrant activation of the Gln61 mutants.

Efficacy and safety of insulin degludec U100 and insulin glargine U100 in combination with meal-time bolus insulin in hospitalized patients with type 2 diabetes: an open-label, randomized controlled study.

The short-term efficacy and safety of insulin degludec U100 (IDeg) in patients with type 2 diabetes have not been reported widely. We compared insulin IDeg and insulin glargine U100 (IGla) for glycemic control and glucose variability in hospitalized patients with type 2 diabetes. In an open-label, multicenter, randomized controlled trial, 74 patients were randomly assigned to either the IDeg (36 patients) or IGla (38 patients) group and were administered with basal-bolus therapy during hospitalization. Following the start of the treatment, on day 11, glucose variability was assessed by continuous glucose monitoring. A fasting blood glucose level of 110 mg/dL and 2-hour postprandial blood glucose level of 180 mg/dL throughout at least one day during the observation period were achieved in 31.3% (10/32) and 30.6% (11/36) of the patients in the IDeg and IGla groups, respectively. The 6-point self-monitoring of blood glucose profiles showed a significant difference between the two groups. On day 7, the intra-day variation was larger in the IDeg group than in the IGla group. The incidence of hypoglycemia or glucose variability was comparable in the two groups. This study suggests that short-term efficacy and safety of IDeg and IGla in patients with type 2 diabetes during the initial phase of basal-bolus therapy were comparable, and these results can help in deciding which treatment to opt for.

Factors associated with patient information sharing among home-visiting nurses in Japan: a cross-sectional study.

BACKGROUND: Home-visiting nurses are expected to enhance their ability to provide adequate nursing care in a relatively isolated work environment. However, the isolated work environment leads to less opportunity to share patient information. We investigated factors relevant to better patient information sharing among home-visiting nurses, which would contribute to the improved care performance of these nurses. METHODS: A cross-sectional study with anonymous self-administered questionnaire was conducted between June 2015 and September 2015 in two districts of Japan. Home-visiting nurses who were working at home health care agencies were recruited. The questionnaires consisted of items on demographic data, job-related variables, communication in the workplace, the current state of patient information sharing, opportunities (or measures) of patient information sharing in the workplace, and job satisfaction. Descriptive analyses were performed on all variables, using the Chi-square test, Fisher's exact test, or Mann-Whitney U-test. Logistic regression analyses were conducted to identify the factors associated with better information sharing, adjusting the years of home-visiting nursing experience as the control variable. RESULTS: Of 762 anonymous self-administered questionnaires were mailed, data from 482 participants who consented to this study and had no missing answer were analyzed. Of the total, 77.2% shared the patients' information. Having a friendly adviser (OR = 2.51, 95% CI = 1.14-5.55, p = 0.023), attending some conferences (OR = 2.32, 95% CI = 1.12-4.82, p = 0.024), joining workshops (OR = 1.89, 95% CI = 1.15-3.10, p = 0.012), and years of home-visiting nursing experience (OR = 1.27, 95% CI = 1.03-1.57, p = 0.025) were significantly associated with sufficient sharing of the information. Nurses sufficiently sharing the information were well satisfied with their job (OR = 5.38, 95% CI =3.19-9.09, p < 0.001) and highly preferred a career in home-visiting nursing care (OR = 5.62, 95% CI =3.41-9.27, p < 0.001). CONCLUSIONS: The results suggested that having opportunities to discuss face-to-face such as at conferences and workshops as well as promoting good relationships among colleagues in the workplace will contribute to better information sharing among home-visiting nurses. Home-visiting nurses with less years of experience need to be supported in order to share the information sufficiently. Additionally, sufficient information sharing was also associated with job satisfaction and preference for home-visiting nursing care, which might lead to job retention for home-visiting nurses.

Loop of Streptomyces Feruloyl Esterase Plays an Important Role in the Enzyme's Catalyzing the Release of Ferulic Acid from Biomass.

Feruloyl esterases (FAEs) are key enzymes required for the production of ferulic acid from agricultural biomass. Previously, we identified and characterized R18, an FAE from Streptomyces cinnamoneus NBRC 12852, which showed no sequence similarity to the known FAEs. To determine the region involved in its catalytic activity, we constructed chimeric enzymes using R18 and its homolog (TH2-18) from S. cinnamoneus strain TH-2. Although R18 and TH2-18 showed 74% identity in their primary sequences, the recombinant proteins of these two FAEs (recombinant R18 [rR18] and rTH2-18) showed very different specific activities toward ethyl ferulate. By comparing the catalytic activities of the chimeras, a domain comprised of residues 140 to 154 was found to be crucial for the catalytic activity of R18. Furthermore, we analyzed the crystal structure of rR18 at a resolution of 1.5 Å to elucidate the relationship between its activity and its structure. rR18 possessed a typical catalytic triad, consisting of Ser-191, Asp-214, and His-268, which was characteristic of the serine esterase family. By structural analysis, the above-described domain was found to be present in a loop-like structure (the R18 loop), which possessed a disulfide bond conserved in the genus Streptomyces Moreover, compared to rTH2-18 of its parental strain, the TH2-18 mutant, in which Pro and Gly residues were inserted into the domain responsible for forming the R18 loop, showed markedly high kcat values using artificial substrates. We also showed that the FAE activity of TH2-18 toward corn bran, a natural substrate, was improved by the insertion of the Gly and Pro residues.IMPORTANCEStreptomyces species are widely distributed bacteria that are predominantly present in soil and function as decomposers in natural environments. They produce various enzymes, such as carbohydrate hydrolases, esterases, and peptidases, which decompose agricultural biomass. In this study, based on the genetic information on two Streptomyces cinnamoneus strains, we identified novel feruloyl esterases (FAEs) capable of producing ferulic acid from biomass. These two FAEs shared high similarity in their amino acid sequences but did not resemblance any known FAEs. By comparing chimeric proteins and performing crystal structure analysis, we confirmed that a flexible loop was important for the catalytic activity of Streptomyces FAEs. Furthermore, we determined that the catalytic activity of one FAE was improved drastically by inserting only 2 amino acids into its loop-forming domain. Thus, differences in the amino acid sequence of the loop resulted in different catalytic activities. In conclusion, our findings provide a foundation for the development of novel enzymes for industrial use.

The role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease: A scoping review protocol.

INTRODUCTION: The number of patients with chronic kidney disease is increasing worldwide; previous studies have suggested that advanced practice nurses, including nurse practitioners and clinical nurse specialists, with expert practice skills can provide high-quality care and solve complex healthcare problems. In general, nurse practitioners are generalist nurses who work as autonomous clinicians with whole personal care. Clinical nurse specialists, in contrast, are nurses with advanced nursing knowledge and skills for individuals or specific populations. Their roles are independent and different; however, similarities exist in their role in potentially improving healthcare outcomes. Although two previous studies described the role of nephrology nurse practitioners, they were systematic reviews, and their outcomes were limited. To clarify the overall aspect of advanced practice nurses' role, it is necessary to extract the studies illustrating advanced practice nurses' practices for patients with chronic kidney disease. OBJECTIVE: This study aims to map the literature describing the role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease. MATERIALS AND METHODS: This scoping review will be conducted using the Joanna Briggs Institute methodology for scoping review. Online databases will be searched across MEDLINE (PubMed), CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science. Only studies published in English will be included, and no date limit will be set. Chronic kidney disease, renal replacement therapy, and advanced practice nurses as keywords and related search terms will be used. Two independent reviewers will screen the title and abstract/full-text; in case of discrepancy, a third reviewer will make the final decision. The results will be extracted and presented following the review question concerning the study characteristics, patients' characteristics, condition of chronic kidney disease, and role of advanced practice nurses.

Medicinal flowers. XXXVIII. structures of acylated sucroses and inhibitory effects of constituents on aldose reducatase from the flower buds of Prunus mume.

The methanolic extract from the flower buds of Prunus mume, cultivated in Zhejiang province, China, showed an inhibitory effect on aldose reductase. From the methanolic extract, five new acylated sucroses, mumeoses F-J, were isolated together with 29 known compounds. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Acylated quinic acid analogs, which are one of the major compounds of the flower buds of P. mume, were shown to substantially inhibit aldose reductase. In particular, mumeic acid-A was found to exhibit a potent inhibitory effect [IC50=0.4 µm].

Hearing impairments caused by genetic and environmental factors.

Impairments of hearing and balance are major problems in the field of occupational and environmental health. Such impairments have previously been reported to be caused by genetic and environmental factors. However, their mechanisms have not been fully clarified. On the other hand, the inner ear contains spiral ganglion neurons (SGNs) in the organ of Corti, which serve as the primary carriers of auditory information from sensory cells to the auditory cortex in the cerebrum. Inner ears also contain a vestibule in the vicinity of the organ of Corti-one of the organs responsible for balance. Thus, inner ears could be a good target to clarify the pathogeneses of sensorineural hearing losses and impaired balance. In our previous studies with c-Ret knock-in mice and Endothelin receptor B (Ednrb) knock-out mice, it was found that syndromic hearing losses involved postnatal neurodegeneration of SGNs caused by impairments of c-Ret and Ednrb, which play important roles in neuronal development and maintenance of the enteric nervous system. The organ of Corti and the vestibule in inner ears also suffer from degeneration caused by environmental stresses including noise and heavy metals, resulting in impairments of hearing and balance. In this review, we introduce impairments of hearing and balance caused by genetic and environmental factors and focus on impairments of SGNs and the vestibule in inner ears as the pathogeneses caused by these factors.

Effect of dulaglutide and long-acting insulin combination therapy in patients with type 2 diabetes: a retrospective observational study.

Objective: The study aimed to evaluate the long-term effects of combination therapy comprising dulaglutide and long-acting insulin, on glycemic control in patients with type 2 diabetes. Methods: This retrospective observational study included 20 patients with type 2 diabetes who underwent blood glucose management with intensive insulin therapy for a limited period. All patients were switched from intensive insulin therapy to combination therapy comprising dulaglutide and long-acting insulin. Hemoglobin A1c was evaluated before and 4, 12, and 24 weeks after starting combination therapy. Continuous glucose monitoring was conducted before and 1 and 24 weeks after starting combination therapy. Results: Hemoglobin A1c levels were significantly reduced after 4, 12, and 24 weeks of combination therapy (- 2.2% ± 0.4%, P < 0.0001; - 3.7% ± 0.8%, P = 0.0003; and - 3.6% ± 0.8%, P = 0.0005, respectively). Glycemic variability (% coefficient of variation) was significantly decreased after 1 and 24 weeks of combination therapy (- 5.7% ± 2.1%, P = 0.011; and - 8.7% ± 2.4%, P = 0.003, respectively) and the percentage of readings and time > 250 mg/dL at 24 weeks was significantly improved (- 2.2% ± 0.8%, P = 0.019). Conclusion: Combination therapy with dulaglutide and long-acting insulin resulted in better blood glucose control than intensive insulin therapy, which persisted for 24 weeks. Combination therapy also reduced blood glucose fluctuations and the number of self-injections needed. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00592-z.

Antidiabetogenic oligostilbenoids and 3-ethyl-4-phenyl-3,4-dihydroisocoumarins from the bark of Shorea roxburghii.

A methanol extract of the bark of Shorea roxburghii (Dipterocarpaceae) was found to inhibit plasma glucose elevation in sucrose-loaded mice. From the extract, three new 3-ethyl-4-phenyl-3,4-dihydroisocoumarins, 1'S-dihydrophayomphenol A(2) (1) and phayomphenols B(1) (2) and B(2) (3), were isolated together with 24 known compounds including 20 stilbenoids and oligostilbenoids. The structures of 1-3 were determined on the basis of their spectroscopic properties as well as of chemical evidences. Among the isolates, (-)-hopeaphenol (6), hemsleyanol D (8), (+)-α-viniferin (15), and (-)-balanocarpol (18) showed inhibitory activity against plasma glucose elevation in sucrose-loaded rats at doses of 100-200mg/kg, p.o. To clarify the mode of action of the antihyperglycemic property, effects of these oligostilbenoids on gastric emptying in mice, those on glucose uptake in isolated intestinal tissues as well as inhibitory activities against rat intestinal α-glucosidase and rat lens aldose reductase were examined.

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study.

Patients with type 2 diabetes who have cardiovascular disease and are receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes. In contrast, glimepiride increases cardiovascular hospitalization when combined with metformin. Here, we assessed the effects of empagliflozin and glimepiride on endothelial function using flow-mediated dilation (FMD). In this prospective, open-label, randomized, parallel-group study, 63 patients with type 2 diabetes received metformin and insulin glargine U100 for 12 weeks. This was followed by additional treatment with empagliflozin or glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (ΔFMDs) at 24 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. The empagliflozin group (n = 33) and glimepiride group (n = 30) showed no significant differences in ΔFMDs (empagliflozin, -0.11 [95%CI: -1.02, 0.80]%; glimepiride, -0.34 [95%CI: -1.28, 0.60]%; P = 0.73). Additionally, changes in glycated hemoglobin were similar between the two groups. However, a significant difference in body weight change was observed (empagliflozin, -0.58 [95%CI: -1.60, 0.43] kg; glimepiride, 1.20 [95%CI: 0.15, 2.26] kg; P = 0.02). Moreover, a body composition analysis revealed that body fluid volume significantly decreased after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, -0.33 ± 0.72 L; P = 0.03). Hence, although empagliflozin did not improve endothelial function compared with glimepiride for patients with type 2 diabetes, it did decrease body fluid volumes. Thus, the coronary-protective effect of empagliflozin is not derived from endothelial function protection, but rather from heart failure risk reduction. Trial registration: This trial was registered on September 13, 2016; UMIN000024001.

Substrate-induced closing of the active site revealed by the crystal structure of pantothenate synthetase from Staphylococcus aureus.

Pantothenate synthetase (PS, EC 6.3.2.1) is the last enzyme in the pantothenate biosynthesis pathway, a metabolic pathway identified as a potential target for new antimicrobials. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Here we report the overexpression, purification, enzyme assay, and tertiary structure of PS from Staphylococcus aureus. PS activity was experimentally confirmed, indicating a k(cat) value comparable to those of enzymes from other organisms. The structures of the apoenzyme and the reaction intermediate (pantoyl adenylate; PA) complex were determined by X-ray crystallography to resolutions of 2.5 and 1.85 A, respectively. Structural analysis indicated that the apoenzyme adopts an open and relatively mobile structure, while the complex structure is closed and entirely rigid. Structural comparison of the apoenzyme and the complex revealed how S. aureus PS undergoes open/close conformational change, and also determined the key interactions with the adenine ring of PA for a hinge bending domain closure. In the complex structure, PA and acetate are bound in the active site. We suggest that the acetate mimics the substrate beta-alanine. Therefore, the complex structure seems to represent a catalytic state poised for in-line nucleophilic attack on PA. These data also offer an alternative strategy for designing novel compounds that selectively inhibit PS activity.

Structure of the apo decarbamylated form of 2,3-diketo-5-methylthiopentyl-1-phosphate enolase from Bacillus subtilis.

2,3-Diketo-5-methylthiopentyl-1-phosphate enolase (DK-MTP-1P enolase), a RuBisCO-like protein (RLP), catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate. The crystal structure of the apo decarbamylated form (E form) of Bacillus subtilis DK-MTP-1P enolase (Bs-DK-MTP-1P enolase) has been determined at 2.3 A resolution. The overall structure of the E form of Bs-DK-MTP-1P enolase highly resembles that of Geobacillus kaustophilus DK-MTP-1P enolase (Gk-DK-MTP-1P enolase), with the exception of a few insertions or deletions and of a few residues at the active site. In the E form of Bs-DK-MTP-1P enolase, Lys150 (equivalent to Lys175 in RuBisCO) at the active site adopts a conformation that is distinct from those observed in the other forms of Gk-DK-MTP-1P enolase. This unusual conformational change appears to be induced by changes in the varphi and psi angles of Gly151, which is conserved in the sequences of the Bs-DK-MTP-1P and Gk-DK-MTP-1P enolases but not in those of RuBisCOs. The loop at 303-312, equivalent to the catalytic loop termed ;loop-6' in RuBisCO, is in a closed conformation in the E form of Bs-DK-MTP-1P enolase. The closed conformation appears to be stabilized by Pro312, which is conserved in the sequences of several RLPs (equivalent to Glu338 in RuBisCO). Based on these results, the characteristic structural features of DK-MTP-1P enolase are discussed.

Crystallization and preliminary X-ray analysis of 2,3-diketo-5-methylthiopentyl-1-phosphate enolase from Bacillus subtilis.

2,3-Diketo-5-methylthiopentyl-1-phosphate enolase (DK-MTP-1P enolase) from Bacillus subtilis was crystallized using the hanging-drop vapour-diffusion method. Crystals grew using PEG 3350 as the precipitant at 293 K. The crystals diffracted to 2.3 A resolution at 100 K using synchrotron radiation and were found to belong to the monoclinic space group P2(1), with unit-cell parameters a = 79.3, b = 91.5, c = 107.0 A, beta = 90.8 degrees. The asymmetric unit contained four molecules of DK-MTP-1P enolase, with a V(M) value of 2.2 A(3) Da(-1) and a solvent content of 43%.

The association of smartphone use and depression in Japanese adolescents.

The aim of this study is to assess the association between smartphone usage and depression in each gender of senior high school students. A cross-sectional study with self-administered questionnaires for 295 high school students, aged 15-19 was conducted in Japan. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Female adolescents used smartphones more hours a day than males. Students who used the smartphones for three hours a day accounted for 44.3% of female students and 22.5% of male students. Female students spent longer hours on online chat, social networking sites (SNS), and Internet browsing. The longer hours they spent for online chat (Odds ratio (OR): 1.74; 95% confidence interval (CI): 1.18-2.56), and SNS (OR: 1.41, 95% CI: 1.04-1.92) were associated with depression. On the other hand, male students spent more hours playing games than female students, and their smartphone use was not correlated with depression. There were gender differences in smartphone usage: female students spent more time on social contacts, whereas males were more likely to use them for entertainment. Therefore, if female students overuse online communication, they may be at a higher risk for depression.

Relationship between pneumatization of lateral recess in the sphenoid sinus and removal of cavernous sinus invasion in pituitary adenomas by endoscopic endonasal surgery.

BACKGROUND: Endoscopic endonasal transsphenoidal surgery (EES) is the gold standard for pituitary adenoma (PA) resection. The sphenoid sinus (SS), a highly variable anatomic structure, is located in the center of the cranial base. It has previously been reported that poor pneumatization of the lateral recess of the SS (LRSS) increases the difficulty level of the surgery and the risk of neural and vascular injury. However, to date no studies have evaluated the association between LRSS volume and PAs removal rate by EES. METHODS: The present study analyzed 23 consecutive patients with new-onset PAs categorized as Knosp Grades 3 and 4 who underwent EES. A retrospective radiographic analysis was conducted on patients undergoing magnetic resonance imaging and high-resolution computed tomography scans. RESULTS: Among PA cases categorized as Knosp 3 and 4, no significant association was found between the whole tumor's resection rate and LRSS volume (R = 0.08, P = 0.70). However, a significant association was found between cavernous sinus (CS) tumors' removal rate and LRSS volume (R = 0.52, P = 0.011). The same results were achieved in PAs with a Knosp Grade 4, with a stronger correlation (R = 0.60, P = 0.014). CONCLUSION: The development of LRSS pneumatization affects the removal rate of CS tumors in PAs. Preoperative analysis of LRSS development should be considered when planning EES against PA with CS invasion.

Analysis of Tumor Angiogenesis and Immune Microenvironment in Non-Functional Pituitary Endocrine Tumors.

Cavernous sinus (CS) invasion is an aggressive behavior exhibited by pituitary neuroendocrine tumors (PitNETs). The cause of CS invasion in PitNETs has not been fully elucidated. The tumor immune microenvironment, known to promote aggressive behavior in various types of tumors, has not been examined for PitNETs. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling is strongly associated with the tumor immune microenvironment. In the present study, these molecular and histopathological characteristics were examined in invasive non-functional PitNETs (NF-PitNETs). Twenty-seven patients with newly diagnosed NF-PitNETs (with CS invasion: 17, without CS invasion: 10) were analyzed by immunohistochemistry for VEGF-A/VEGFR1 and 2, hypoxia-inducible Factor (HIF), tumor-infiltrating lymphocytes, immunosuppressive cells including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), and immune checkpoint molecules. Previously validated tumor proliferation markers including mitotic count, Ki-67 index, and p53 were also analyzed for their expressions in NF-PitNETs. VEGF-A and VEGFR1 were expressed on not only vascular endothelial cells, but also on tumor cells. The expressions of VEGF-A and VEGFR1 were significantly higher in NF-PitNETs with CS invasion. The number of TAMs and the expression of PD-L1 were also significantly higher in NF-PitNETs with CS invasion than in NF-PitNETs without CS invasion. The high expression of VEGF-A and VEGFR1 and associated immunosuppressive microenvironment were observed in NF-PitNETs with CS invasion, suggesting that a novel targeted therapy can be applied.

Crystal structure of 5-methylthioribose 1-phosphate isomerase product complex from Bacillus subtilis: implications for catalytic mechanism.

The methionine salvage pathway (MSP) plays a crucial role in recycling a sulphahydryl derivative of the nucleoside. Recently, the genes and reactions in MSP from Bacillus subtilis have been identified, where 5-methylthioribose 1-phosphate isomerase (M1Pi) catalyzes a conversion of 5-methylthioribose 1-phosphate (MTR-1-P) to 5-methylthioribulose 1-phosphate (MTRu-1-P). Herein, we report the crystal structures of B. subtilis M1Pi (Bs-M1Pi) in complex with its product MTRu-1-P, and a sulfate at 2.4 and 2.7 A resolution, respectively. The electron density clearly shows the presence of each compound in the active site. The structural comparison with other homologous proteins explains how the substrate uptake of Bs-M1Pi may be induced by an open/closed transition of the active site. The highly conserved residues at the active site, namely, Cys160 and Asp240 are most likely to be involved in catalysis. The structural analysis sheds light on its catalytic mechanism of M1Pi.