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Biomedical subjects

L Jin

Publications and source records attributed to L Jin.

At least 271 records · Page 15Linked to original sources
PubMed1998

[The diversity of human hematopoietic stem/progenitor cells: IX. Cell-cycles kinetics related macromolecules DNA, RNA and protein contents in CD34+ hematopoietic cells of human bone marrow].

DNA, RNA and PRO comprise the bulk of macromolecules in cells, which have been proven to play an important role in regulating cell cycle transverse capacity, cell division, growth, and size. Simultaneous analysis of these moieties could provide more comprehensive and accurate information on cell cycle kinetics. In this study, DNA, RNA and PRO contents related to cell cycle kinetics in CD34+ hematopoietic cells of human bone marrow were measured to understanding the cell cycle kinetic features in CD34+ hematopoietic cells. For this reason, CIMS-100 immunomagnetic isolator, a novel isolation system, was used to enrich efficiently CD34+ hematopoietic cells from human bone marrow. The purity of enriched CD34+ hematopoietic cells determined by both FACS and APAAP staining is ranging from 90%-95%. Cellular DNA, RNA and PRO were stained with fluorochromes propidium iodide, pyronin Y and fluorescein isothiocyante respectively The fluorescence intensities reflecting the DNA, RNA and PRO content of individual cell were analyzed in FACS can by different excitation wavelengthes. DNA, RNA and PRO contents in CD34+ hematopoietic cells were far lower than these of bone marrow mononuclear cells, only being 34 +/- 3% (DNA), 48 +/- 21% (RNA) and 62 +/- 14% (PRO) of BMMNCs respectively. Collectively, these data combined with previous results from both ours and others indicated that CD34+ hematopoietic cells are indeed an unique cell population, not only in reconstitute of hematopoietic and immunological functions, but also in cell cycle kinetics. This is, to our knowledge, the first detailed report on the analysis of DNA, RNA and PRO contents related to cell cycle kinetics in CD34+ hematopoietic cells. And the results provide more direct evidence that the majority of CD34+ hematopoietic cells are in resting state.

Antigens, CD34↗
PubMed1998

[Study of adsorptive voltammetry for adrenaline on carbon paste electrode].

Adrenaline is determined by adsorptive voltammetry using a carbon paste electrode in a base solution of 0.5 mol.L-1 H2SO4. The peak potential of anode is 0.58 V (vs. SCE). There is a good linear relationship between the peak current and the concentration of adrenaline in the range of 5.0 x 10(-9)-1.0 x 10(-4) mol.L-1. The detection limit of the method is 2.5 x 10(-9) mol.L-1. The recovery is 93.75%-103.33%, and the relative standard deviation is 3.1% (n = 12). The adrenaline hydrochloride injection has been determined with good results by this method. The possible reaction mechanism is discussed. The electrode reaction of adrenaline is irreversible process with two electrons and two protons on the carbon paste electrode.

Electrodes↗
PubMed1998

Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors.

Thyroid neoplasms represent a broad spectrum of tumors with different biologic behaviors. The majority of these tumors can be readily diagnosed by characteristic histopathologic features, but the distinction between follicular adenomas and follicular carcinomas can be difficult. Recent studies with cell cycle proteins such as p27kip1 (p27), a cell cycle inhibitory protein, and Ki-67, a proliferation marker, suggest that these markers might be useful in predicting the behavior of various neoplasms. We analyzed 95 thyroid lesions (16 follicular adenomas, 23 follicular carcinomas, 22 papillary carcinomas, 27 anaplastic carcinomas, plus 7 non-neoplastic thyroids [NNTs], used as a control group) for expression of p27 and Ki-67 by immunostaining. The distribution of immunoreactivity was analyzed by quantifying nuclear staining in each case without knowledge of the diagnosis or outcome. Clinical history and follow-up information were obtained by chart review. There were significant differences in the expression of p27 between follicular adenomas (labeling index [LI] = 47.9+/-5.6) and follicular carcinomas (LI = 15.7+/-2.0). Papillary carcinomas (LI = 11.6+/-3.0) and anaplastic carcinomas (LI = 9.4+/-1.7) had p27 LIs similar to that of follicular carcinomas; the NNT group had the highest p27 LI (74.1+/-4.9). The Ki-67 LI of anaplastic carcinomas (57.6+/-3.8) was more than threefold greater than that of any other group. Logistic regression showed that p27 was effective in distinguishing follicular adenomas from follicular carcinomas (P = .0056) and that Ki-67 could also distinguish follicular adenomas from follicular carcinomas (P = .0060). Analysis of follicular carcinomas with and without metastases showed significantly higher expression of Ki-67 in patients with metastases (P = .0019). These results indicate that antibodies to p27 and Ki-67 might be useful in distinguishing between thyroid neoplasms that are difficult to diagnose by the usual histopathologic criteria.

Adenocarcinoma, Follicular↗
PubMed1997

The anticoagulant activation of antithrombin by heparin.

Antithrombin, a plasma serpin, is relatively inactive as an inhibitor of the coagulation proteases until it binds to the heparan side chains that line the microvasculature. The binding specifically occurs to a core pentasaccharide present both in the heparans and in their therapeutic derivative heparin. The accompanying conformational change of antithrombin is revealed in a 2.9-A structure of a dimer of latent and active antithrombins, each in complex with the high-affinity pentasaccharide. Inhibitory activation results from a shift in the main sheet of the molecule from a partially six-stranded to a five-stranded form, with extrusion of the reactive center loop to give a more exposed orientation. There is a tilting and elongation of helix D with the formation of a 2-turn helix P between the C and D helices. Concomitant conformational changes at the heparin binding site explain both the initial tight binding of antithrombin to the heparans and the subsequent release of the antithrombin-protease complex into the circulation. The pentasaccharide binds by hydrogen bonding of its sulfates and carboxylates to Arg-129 and Lys-125 in the D-helix, to Arg-46 and Arg-47 in the A-helix, to Lys-114 and Glu-113 in the P-helix, and to Lys-11 and Arg-13 in a cleft formed by the amino terminus. This clear definition of the binding site will provide a structural basis for developing heparin analogues that are more specific toward their intended target antithrombin and therefore less likely to exhibit side effects.

Anticoagulants↗
PubMed1997

Synthesis and DNA binding studies of cobalt (III) mixed-polypyridyl complex.

The complex of Co(phen)2dppz3+ (where phen is ophenanthroline, and dppz is dipyrido [3, 2-a: 2', 3'-c] phenazine) has been synthesized. This complex was characterized by elemental analysis, molar conductivity, IR and 1H NMR spectroscopy. The interaction of the complex with calf thymus DNA has been studied using absorption and emission spectroscopy, DNA melting techniques, cyclic voltammetric, viscosity, and electrophoresis measurements. The compound shows absorption hypochromicity, fluorescence enhancement, DNA melting temperature, and the specific viscosity increased when binding to calf thymus DNA. CV measurement shows that the shifts in oxidation-reduction potential and change in peak current with addition of DNA. The complex is also shown to be more efficient photosensitisers for single strand breaks in plasmid DNA.

Cobalt↗
PubMed1997

Gene therapy in hypertension: adenovirus-mediated kallikrein gene delivery in hypertensive rats.

Tissue kallikrein has been shown to play a role in blood pressure regulation, and abnormalities in the kallikreinkinin system are considered to be a factor in the pathogenesis of hypertension. To elucidate the potential therapeutic effects of kallikrein gene delivery in hypertension, an adenoviral vector containing the human tissue kallikrein gene under the control of a cytomegalovirus promoter, Ad.CMV-cHK, was intravenously injected into spontaneously hypertensive rats (SHR). A single injection of Ad.CMV-cHK into SHR caused a sustained delay in the increase in blood pressure from day 2 to day 41 post injection, as compared to control rats receiving Ad.CMV-LacZ adenovirus. Adenovirus-mediated kallikrein gene delivery had no effect on the blood pressure of normotensive Wistar-Kyoto rats. Human tissue kallikrein mRNA was detected in the liver, kidney, spleen, adrenal gland, and aorta. Immunoreactive human tissue kallikrein can be detected in sera and urine of rats receiving kallikrein gene delivery. Human tissue kallikrein in rat serum was at the highest level 5 days post injection, and the level declined gradually. Urinary kinin and cGMP levels were significantly increased in rats receiving kallikrein gene delivery compared to Ad.CMV-LacZ control rats. These results show that adenovirus-mediated delivery of human tissue kallikrein results in high-efficiency expression and blood pressure reduction in SHR. Application of adenovirus-mediated systemic expression of the tissue kallikrein gene may provide a unique way of delivering the gene product into the vasculature and could have important therapeutic implications in treating hypertension.

Adenoviridae↗
PubMed1997

A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year.

Neuronal plasticity plays a very important role in brain adaptations to environmental stimuli, disease, and aging processes. The kainic acid model of temporal lobe epilepsy was used to study the long-term anatomical and biochemical changes in the hippocampus after seizures. Using Northern blot analysis, immunocytochemistry, and Western blot analysis, we have found a long-term elevation of the proconvulsive opioid peptide, enkephalin, in the rat hippocampus. We have also demonstrated that an activator protein-1 transcription factor, the 35-kDa fos-related antigen, can be induced and elevated for at least 1 year after kainate treatment. This study demonstrated that a single systemic injection of kainate produces almost permanent increases in the enkephalin and an activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the rat hippocampus, and it is likely that these two events are closely associated with the molecular mechanisms of induction of long-lasting enhanced seizure susceptibility in the kainate-induced seizure model. The long-term expression of the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus also suggests an important role in the recurrent seizures of temporal lobe epilepsy.

Animals↗
PubMed1997

Heparin-dependent modification of the reactive center arginine of antithrombin and consequent increase in heparin binding affinity.

Antithrombin, the principal plasma inhibitor of coagulation proteinases, circulates in a form with low inhibitory activity due to partial insertion of its reactive site loop into the A-beta-sheet of the molecule. Recent crystallographic structures reveal the structural changes that occur when antithrombin is activated by the heparin pentasaccharide, with the exception of the final changes, which take place at the reactive center itself. Here we show that the side chain of the P1 Arg of alpha-antithrombin is only accessible to modification by the enzyme peptidylarginine deiminase on addition of the heparin pentasaccharide, thereby inactivating the inhibitor, whereas the natural P1 His variant, antithrombin Glasgow, is unaffected, indicating that only the P1 Arg becomes accessible. Furthermore, the deimination of P1 Arg converts antithrombin to a form with 4-fold higher affinity for the heparin pentasaccharide, similar to the affinity found for the P1 His variant, due to a lowered dissociation rate constant for the antithrombin-pentasaccharide complex. The results support the proposal that antithrombin circulates in a constrained conformation, which when released, in this study by perturbation of the bonding of P1 Arg to the body of the molecule, allows the reactive site loop to take up the active inhibitory conformation with exposure of the P1 Arg.

Antithrombin III↗
PubMed1997

Expression of interleukin-1beta in human breast carcinoma.

BACKGROUND: Interleukin 1beta (IL-1beta) is a multifunctional cytokine that up-regulates the inflammatory response. It is not known whether IL-1beta plays a major role in human malignancy. To determine whether IL-1beta might be involved in breast carcinoma progression, the authors measured the IL-1beta content in tissue extracts from >200 invasive breast carcinomas and smaller numbers of ductal carcinoma in situ (DCIS) and benign lesions. METHODS: IL-1beta content was measured by an enzyme-linked immunoadsorbent assay and analyzed to determine whether these values were correlated with the contents of scatter factor (SF) (an invasogenic and angiogenic cytokine), von Willebrand's factor (VWF) (a marker of endothelium), thrombospondin-1 (TSP1) (an antiadhesive and antiangiogenic glycoprotein), and tumor necrosis factor-alpha (TNF alpha) (another proinflammatory cytokine). Studies were also performed to determine whether IL-1beta content was correlated with other pathologic and immunochemical variables that have been utilized or proposed as prognostic indicators for breast carcinoma. RESULTS: The most important findings of these studies were: 1) immunoreactive IL-1beta was detected in approximately 90% of invasive breast carcinomas; 2) IL-1beta levels were significantly higher in invasive carcinomas than in a group of DCIS and benign lesions; 3) high IL-1beta content in invasive carcinomas was significantly associated with higher contents of SF, VWF, and TSP1, but not TNF alpha; and 4) there was a trend toward higher IL-1beta content in invasive carcinomas with a group of other parameters that suggest a biologically more aggressive tumor (estrogen receptor negativity, high tumor grade, p53 positivity, and bcl-2 negativity); and the proportion of invasive tumors with these characteristics was significantly increased in a subgroup of tumors having very high IL-1beta content. The authors also found a correlation between high IL-1beta content and CD68 positivity, suggesting that macrophages may account for some of the IL-1beta present in human breast carcinoma tissue. CONCLUSIONS: These findings suggest that significant titers of IL-1beta are present within the microenvironment of most breast carcinomas and that a high IL-1beta content is often associated with tumor invasiveness and with other pathologic features suggestive of an aggressive tumor biology.

Biomarkers↗
PubMed1997

Evaluation of clinical and environmental anti-estrogens with human estrogen receptor expressed in Saccharomyces cerevisiae: a novel role for ABC-cassette transporters in mediating anti-estrogenic activity.

The effectiveness of anti-estrogens in treating estrogen-dependent diseases is limited by the acquired resistance of some diseases to anti-estrogens. This effect could occur by the export of anti-estrogens by cell membrane transport proteins. To study this phenomenon we have expressed human estrogen receptor (hER) and an estrogen-sensitive reporter in wild-type yeast and two transport-defective strains. In the wild-type strain, the most effective anti-estrogen was nafoxidine. 4-Hydroxy tamoxifen and clomiphene were inactive whereas tamoxifen had significant inhibitory activity in the wild-type strain. Using a strain missing the ABC-cassette transporter Snq2, clomiphene had anti-estrogenic activity. 4-Hydroxy tamoxifen had anti-estrogenic activity only in yeast lacking the transporter Pdr5. Whole cell binding assays indicated that 4-hydroxy tamoxifen is exported by Pdr5. Environmental chemicals such as polychlorinated biphenyls function as partial estrogens and anti-estrogens in yeast. In the absence of Pdr5 or Snq2, the estrogenic activity of 4-hydroxy, 2',4',6'-trichloro biphenyl (3-PCB) was substantially reduced in comparison to its activity in the wild-type strain. Interestingly, the antiestrogenic activity of 3-PCB was equivalent in the wild-type and transporter-defective strains. Our results suggest a novel role for ABC-cassette transporters in regulating the activity of clinical and environmental anti-estrogens.

ATP-Binding Cassette Transporters↗
PubMed1997

Several synthetic chemicals inhibit progesterone receptor-mediated transactivation in yeast.

The human progesterone receptor (hPR) B-form and a progesterone-sensitive reporter were expressed in yeast and used to screen a library of synthetic chemicals for their ability to function as agonists or antagonists of hPR. The transcriptional activity of hPR was not increased in the presence of over 40 individual chemicals. Seven chemicals decreased progesterone-dependent activity in yeast. The most effective chemicals were 6-hydroxychrysene, 1-hydroxypyrene, 4-hydroxy, 2',4',6'-trichloro biphenyl, and 4-hydroxy, 2',3',4',5'-tetrachloro biphenyl. The decrease of progesterone-mediated transactivation strongly correlated with their displacement of [3H]progesterone from hPR. The absence of the hydroxyl group on the above chemicals completely abolished their inhibitory activity. The other chemicals which decreased progesterone activity were endosulfan II, endosulfan sulfate, and lindane. These chemicals did not inhibit [3H]progesterone binding, suggesting that they inhibit progesterone action by interacting with a region of hPR distinct from binding [3H]progesterone or by a mechanism independent of hPR. These results highlight the utility of yeast for screening hormonally-active chemicals. In addition, hydroxylation appears to be essential for the interaction of some chemicals with hPR.

Humans↗
PubMed1997

Expression of scatter factor and c-met receptor in benign and malignant breast tissue.

BACKGROUND: Scatter factor (SF), also known as hepatocyte growth factor, is an angiogenic cytokine that stimulates epithelial cell motility and invasion. Its receptor is a transmembrane tyrosine kinase encoded by the c-met protooncogene. Several prior experimental and clinical studies have suggested that SF might play a role in the development and progression of breast carcinoma. To investigate the possible involvement of SF and c-met in the evolution of breast carcinoma, the authors studied their expression in sections of human breast tissue. METHODS: A variety of paraffin embedded tissue specimens (of normal breast tissue tissue, benign hyperplasia, ductal carcinoma-in-situ [DCIS], and invasive ductal carcinoma) from 125 patients were immunoperoxidase-stained using specific antisera against SF and c-met. The staining intensities of epithelial mammary cells were scored semiquantitatively, and the staining scores were analyzed as a function of tissue type. In addition, in situ hybridization to detect SF mRNA was performed for a small number of cancer sections. RESULTS: Specific SF staining was observed in tumor cells, normal cell types (epithelium and vascular smooth muscle), and acellular stroma, whereas c- met staining was observed in tumor cells and normal cell types but not in stroma. Analysis of the staining scores of epithelial mammary cells revealed several patterns: (1) SF and c-met staining scores each increased in the following order: normal breast/benign hyperplasias (lowest) --> DCIS (higher) --> invasive carcinoma (highest); (2) normal-appearing mammary ducts and lobules in invasive cancer sections showed less SF and c-met staining than tumor cells in the same specimens but more staining than normal ducts and lobules in sections of normal breast tissue and benign hyperplasia; (3) within the DCIS and invasive cancer groups, SF and c-met staining scores were correlated; and (4) among 40 consecutive cases of DCIS, higher levels of SF and c-met staining showed a trend toward association with other features suggestive of aggressive tumor biology (comedo histology, high nuclear grade, p53 positivity, and bcl-2 negativity). In situ hybridization analysis revealed that the same cell types that expressed SF protein (including tumor cells) also expressed SF mRNA transcripts. CONCLUSIONS: SF and c-met are overexpressed in breast carcinoma as compared with benign breast tissue, and they tend to be coexpressed in cancerous tissue. These findings are consistent with the idea that the SF:c-met ligand:receptor pair may have a role in breast carcinoma progression.

Breast↗
PubMed1997

Tamoxifen-induced estrogen receptor up-regulation in mammary tumor cells is not related to growth inhibition.

Treatment of estrogen receptor (ER)-positive mammary tumors with tamoxifen produces a dramatic accumulation of ER in the cell nucleus. We investigated whether this phenomenon might be related to the antitumor activity of the drug. Five tamoxifen derivatives for which an influence on MCF-7 cell growth had previously been established were tested for that purpose; two of them inhibited growth, one was growth-stimulatory, and the remaining two were without significant effect. At 1 microM all compounds up-regulated ER in the cell nucleus after 3 days of culture, suggesting that the ER accumulation does not predict the response to tamoxifen treatment. An analysis of a tamoxifen-resistant clone (RT x 6 cells) under similar experimental conditions led to the same conclusion: the ER level significantly increased in the presence of tamoxifen and its 4-hydroxy metabolite.

Antineoplastic Agents, Hormonal↗
PubMed1997

Localization of calbindin-D28k in normal and incised mouse skin: immunohistochemical and immunoblot analysis.

The subcellular localization of the protein calbindin-D28k in normal and incised mouse skin was investigated by immunohistochemical staining and immunoblot analysis. In normal skin, the presence of calbindin-D28k was demonstrated in both the nucleus and the cytoplasm of epidermal keratinocytes. Higher levels of calbindin-D28k were detected in the nucleus than in the cytoplasm. Following incision, the levels of calbindin-D28k were significantly decreased in epidermal keratinocytes, particularly in the nucleus, compared with those in normal skin. The immunohistochemical staining and immunoblot analysis showed nuclear calbindin-D28k to be decreased or absent during a 10-day observation period following skin incision. Based on these findings, it is suggested that calbindin-D28k may be distributed in both the nucleus and cytoplasm of epidermal keratinocytes in mice, and this protein may be involved in active cell proliferation of the epidermis induced by skin incision.

Animals↗
PubMed1997

Metabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in rats.

The chemoprotective effects of diallyl sulfide (DAS), a flavor component of garlic, have been attributed to its inhibitory effects on CYP2E1-mediated bioactivation of certain carcinogenic chemicals. In addition to being a competitive inhibitor of CYP2E1 in vitro, DAS is known to cause irreversible inhibition of CYP2E1 in rats in vivo. The latter property is believed to be mediated by the DAS metabolite diallyl sulfone (DASO2), which is thought to be a mechanism-based inhibitor of CYP2E1, although the underlying mechanism remains unknown. In order to investigate the nature of the reactive intermediate(s) responsible for the inactivation of CYP2E1 by DAS and its immediate metabolites, the present studies were carried out to detect and identify potential glutathione (GSH) conjugates of DAS and its metabolites diallyl sulfoxide (DASO) and DASO2. By means of ionspray LC-MS/MS, ten GSH conjugates were identified in bile collected from rats dosed with DAS, namely: S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]glutathione (M1, M2; diastereomers), S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]-glutathione (M5), S-[2-(S'-allyl-S'-dioxomercapto)-1-(hydroxymethyl)ethyl]glutathion e (M3, M4; diastereomers), S-[3-(S'-allylmercapto)-2-hydroxypropyl]glutathione (M6), S-(3-hydroxypropyl)-glutathione (M7), S-(2-carboxyethyl)glutathione (M8), allyl glutathionyl disulfide (M9), and S-allylglutathione (M10). With the exception of M6, all of the above GSH conjugates were detected in the bile of rats treated with DASO, while only M3, M4, M5, M7, M8, and M10 were found in the bile of rats treated with DASO2. Experiments conducted in vitro showed that GSH reacted spontaneously with DASO to form conjugates M9 and M10, and with DASO2 to form M10. In the presence of NADPH and GSH, incubation of DAS with cDNA-expressed rat CYP2E1 resulted in the formation of metabolites M6, M9, and M10, while incubation with DASO led to the formation of M3, M4, M5, M9, and M10. When DASO2 acted as substrate, CYP2E1 generated only conjugates M3, M4, M5, and M10. These results indicate that while DAS and DASO undergo extensive oxidation in vivo at the sulfur atom, the allylic carbon, and the terminal double bonds, CYP2E1 preferentially catalyzes oxidation of the sulfur atom to form the sulfoxide and the sulfone (DASO and DASO2). However, it appears that the end product of this sequence, namely, DASO2, undergoes further CYP2E1-mediated activation of the olefinic pi-bond, a reaction which transforms many terminal olefins to potent mechanism-based P450 inhibitors. We hypothesize, therefore, that it is this final metabolic event with DASO2 which leads to autocatalytic destruction of CYP2E1 and which is mainly responsible for the chemoprotective effects of DAS in vivo.

Allyl Compounds↗
PubMed1997

Detection of BK polyomavirus genotypes in healthy and HIV-positive children.

Urine samples from 211 community children (3-7 years age), from 33 HIV type-1 infected children and from 56 HIV-negative children were collected and analyzed for the presence of BK virus (BKV) DNA by PCR. PCR amplifications were carried out using primers specific for the BKV structural region VP1. We also investigated the distribution of BKV subtypes by a restriction fragment polymorphism assay (RFLP). We demonstrated BKV DNA in 3.8% of 211 community children with a higher prevalence of subtype I. In HIV-1 positive children we detected BKV DNA in 2 urine samples (6%) out of 33, both belonging to subtype I. The HIV-negative cluster did not show any positivity to BKV DNA. The results confirm a more frequent primary BKV infection in children of 3-5 years of age and a higher prevalence in hospitalized children affected by HIV-1. The most relevant finding was that among both the community and HIV-1 positive children the subtype I was the most frequently detected.

BK Virus↗
PubMed1997

Crystal structure of calcium bound domain VI of calpain at 1.9 A resolution and its role in enzyme assembly, regulation, and inhibitor binding.

The three dimensional structure of calcium-bound domain VI of porcine calpain has been determined to 1.9 A resolution. The crystal structure reveals five EF-hands, one more than previously suggested. There are two EF-hand pairs, one pair (EF1-EF2) displays an 'open' conformation and the other (EF3-EF4) a 'closed' conformation. Unusually, a calcium atom is found at the C-terminal end of the calcium binding loop of EF4. With two additional residues in the calcium binding loop, the fifth EF-hand (EF5) is in a 'closed' conformation. EF5 pairs up with the corresponding fifth EF-hand of a non-crystallographically related molecule. Considering the EF5's role in a homodimer formation of domain VI, we suggest a model for the assembly of heterodimeric calpain. The crystal structure of a Ca2+ bound domain VI-inhibitor (PD150606) complex has been refined to 2.1 A resolution. A possible mode for calpain inhibition is discussed.

Acrylates↗