Search PubMed⌕ Search

Biomedical subjects

J C Madsen

Publications and source records attributed to J C Madsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mechanisms of tolerance induction and prevention of cardiac allograft vasculopathy in miniature swine: the effect of augmentation of donor antigen load.

OBJECTIVE: Cotransplantation of a donor kidney along with a heart allograft can induce tolerance to both organs and prevent cardiac allograft vasculopathy in miniature swine. To determine whether the tolerogenic effect of donor kidney cotransplantation was due to an effect specific to the kidney graft or to an increase in donor antigen load, we compared heart-kidney recipients with recipients receiving two class I disparate hearts or with recipients receiving donor peripheral mononuclear cells at the time of isolated heart transplantation. METHODS: Recipients of major histocompatibility complex class I disparate allografts received 12 days of cyclosporine (INN: cyclosporin; 10-13 mg/kg administered intravenously on days 0-11). Group 1 animals received a heart alone (n = 5). Group 2 animals received heart and kidney allografts (n = 4). Group 3 animals received two major histocompatibility complex-matched heart allografts (n = 4). Two double-heart recipients were thymectomized 21 days before transplantation. Group 4 animals received a heart allograft and an infusion of high-dose donor peripheral blood leukocytes (2.5 x 10(9) cells/kg, n = 2). RESULTS: Vasculopathy developed in group 1 recipients and the allografts were rejected within 55 days. Group 2 recipients accepted their heart and kidney allografts indefinitely without vasculopathy. Euthymic recipients from group 3 accepted their hearts long-term (>190 and >197 days), but vascular lesions developed. In thymectomized recipients from group 3, the hearts were rejected in 63 and 96 days with severe vasculopathy. Group 4 recipients demonstrated transient macrochimerism but their hearts were rejected within 47 and 63 days. CONCLUSIONS: The beneficial effects of donor kidney cotransplantation on cardiac allograft survival and prevention of cardiac allograft vasculopathy are likely to involve both an increase in donor antigen load and an effect specific to the kidney allograft.

Animals↗
PubMed1999

The effect of thymectomy on tolerance induction and cardiac allograft vasculopathy in a miniature swine heart/kidney transplantation model.

BACKGROUND: We have previously demonstrated that MHC class I disparate hearts transplanted into miniature swine treated with a short course of cyclosporine developed florid cardiac allograft vasculopathy (CAV) and were rejected within 55 days. However, when a donor-specific kidney is cotransplanted with the heart allograft, recipients become tolerant to donor antigen and accept both allografts long-term without the development of CAV. In the present study, we have investigated the role of the host thymus in the induction of tolerance and prevention of CAV in heart/kidney recipients. METHODS: Total thymectomies were performed in six animals (postoperative day [POD]-21), which on day 0 received either an isolated MHC class I disparate heart allograft (n=3) or combined class I disparate heart and kidney allografts (n=3), followed in both cases by a 12-day course of cyclosporine (POD 0-11). Graft survival and the development of CAV in these thymectomized recipients were compared to the same parameters in non-thymectomized, cyclosporine-treated recipients bearing either class I disparate heart allografts (n=5) or heart and kidney allografts (n=4). RESULTS: In the group of animals bearing isolated class I disparate heart allografts, the thymectomized recipients rejected their allografts earlier (POD 8, 22, 27) than the non-thymectomized recipients (POD 33,35,45,47,55). The donor hearts in both the thymectomized and non-thymectomized animals developed florid CAV. In the group of animals bearing combined class I disparate heart and kidney allografts, the nonthymectomized recipients accepted both donor organs long term with no evidence of CAV. In contrast, none of the thymectomized heart/kidney recipients survived >100 days, and they all developed the intimal proliferation of CAV. CONCLUSION: Thymic-dependent mechanisms are necessary for the induction of acquired tolerance and prevention of CAV in porcine heart/kidney recipients.

Animals↗
PubMed1999

Epithelioid and spindle-celled leiomyosarcoma of the heart. Report of 2 cases and review of the literature.

BACKGROUND: Primary cardiac leiomyosarcomas are rare. Isolated reported cases and small series generally describe spindle-celled, high-grade tumors with poor short-term survival; however, the pathologic features of many of these tumors are incompletely documented. The authors report in detail the clinicopathologic features of 2 relatively low-grade epithelioid and spindle-celled primary cardiac leiomyosarcomas. METHODS: Cases 1 and 2 were studied using standard histochemical and immunohistochemical techniques, and case 1 was examined by electron microscopy. The literature was reviewed with regard to primary cardiac leiomyosarcomas. RESULTS: Both tumors showed epithelioid and spindle-celled areas. The tumor in case 1 was low grade, and the tumor in case 2 was predominately low grade with a high-grade focus. A review of 28 reported cases revealed a wide age range (mean, 43 years), equal male-to-female ratio, and a predilection for the left atrium (48%). Follow-up of reported cases with fewer than 5 mitoses per 10 high-power fields showed a mean survival of 22 months compared with a 9-month mean survival for all others. CONCLUSIONS: Short-term follow-up of reported cases of high-grade cardiac leiomyosarcoma suggests a poor prognosis. Long-term follow-up in our case 2, along with follow-up of reported cases that were histologically similar to our cases, suggests that cardiac leiomyosarcomas with low-grade features or mixed low- and high-grade features also have a poor overall long-term survival, with a high rate of local recurrence and systemic spread.

Adult↗
PubMed1998

Creation of the "thymoheart" allograft: implantation of autologous thymus into the heart prior to procurement.

BACKGROUND: A state of tolerance may be more easily achieved if fully vascularized and functional donor thymus is transferred to the recipient at the time of whole organ transplantation. METHODS: A composite "thymoheart" allograft was created by implanting autologous thymus into a donor heart 60-90 days before organ procurement. Successful intracardiac engraftment of autologous thymus was documented by histology and by flow cytometric analysis. RESULTS: Histology of the thymic autografts at explantation revealed viable thymus with preservation of normal thymic architecture. Cells retrieved from thymic autografts 60 days after implantation exhibited the same MHC class I and class II staining profiles by flow cytometry as cells taken from the residual native thymus. CONCLUSION: We have created a novel composite organ that confers vascularized and functional donor thymus to heart allograft recipients at the time of transplantation without affecting cardiac function.

Animals↗
PubMed1998

Transplantation tolerance prevents cardiac allograft vasculopathy in major histocompatibility complex class I-disparate miniature swine.

BACKGROUND: The mechanisms and treatment of cardiac allograft vasculopathy (CAV) remain elusive. We have used partially inbred miniature swine to determine the role of class I MHC antigens in the pathogenesis of CAV and to determine whether acquired tolerance to donor antigen can prevent the development of CAV in large animals. METHODS: Previous studies demonstrated that miniature swine treated with 12 days of cyclosporine (CsA) after the transplantation of MHC class I-disparate kidney allografts all became tolerant to the donor kidneys and survived indefinitely. In the present study, heart allografts were transplanted across the same MHC class I disparity in CsA-treated swine. RESULTS: Unlike kidney allografts, heart allografts were rejected in 33-55 days. By postoperative day 28, all cardiac allografts had developed the intimal proliferation characteristic of CAV. When hearts and kidneys from the same donors were transplanted simultaneously into class I-disparate, CsA-treated recipients, the hosts became tolerant to their cardiac allografts and survived long-term. Furthermore, none of the hearts from the combined heart/kidney recipients developed evidence of CAV. Thus, this report demonstrates that: (1) MHC class I antigens play an important role in the pathogenesis of CAV, (2) the specific unresponsiveness to donor class I antigen induced by a class I-disparate kidney protects a heart transplanted from the same organ donor, and (3) the induction of acquired tolerance prevents the development of CAV. CONCLUSION: These findings in a preclinical system establish the significance of antigen-dependent mechanisms in the pathogenesis of CAV and underscore the importance of achieving tolerance in clinical transplantation.

Animals↗
PubMed1998

Risk of reoperative valve replacement for failed mitral and aortic bioprostheses.

BACKGROUND: One factor influencing the choice of mechanical versus bioprosthetic valves is reoperation for bioprosthetic valve failure. To define its operative risk, we reviewed our results with valve reoperation for bioprosthetic valve failure. METHODS: Records of 400 consecutive patients having reoperative mitral, aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to March 1997 were reviewed. RESULTS: Reoperations were for failed bioprosthetic mitral valves in 219 patients, failed aortic valves in 153 patients, and failed aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute endocarditis, 153 operations (38%) were nonelective. One hundred nine patients (27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass grafting. The incidence of death in the mitral, aortic, and double-valve groups was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of prolonged postoperative hospital stay (>14 days) was, respectively, 57 (26.0%), 41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective, isolated, first-time valve reoperation died. Multivariable predictors (p < 0.05) of hospital death were age greater than 65 years, male sex, renal insufficiency, and nonelective operation; and predictors of prolonged stay were acute endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated pulmonary artery systolic pressure. CONCLUSIONS: Reoperative bioprosthetic valve replacement can be performed with acceptable mortality and hospital stay. The best results are achieved with elective valve replacement, without concurrent cardiac procedures.

Adult↗
PubMed1998

Repair of postinfarction ventricular septal defects.

Postinfarction ventricular septal defects complicate approximately 1% to 2% of cases of acute myocardial infarction and account for about 5% of early deaths after myocardial infarction. By differentiating the surgical treatment of these acquired lesions from the surgical approaches used to repair congenital ventricular septal defects and realizing the significance of differing anatomic locations of postinfarction ventricular septal defects, techniques have been developed that have improved salvage of patients suffering this catastrophic complication of myocardial infarction. The principles underlying these surgical techniques include (1) expeditious establishment of total cardiopulmonary bypass with moderate hypothermia and meticulous attention to myocardial protection; (2) transinfarct approach to ventricular septal defect with the site of ventriculotomy determined by the location of the transmural infarction; (3) thorough trimming of the left ventricular margins of the infarct back to viable muscle to prevent delayed rupture of the closure; (4) conservative trimming of the right ventricular muscle as required for complete visualization of the margins of the defect; (5) inspection of the left ventricular papillary muscles and concomitant replacement of the mitral valve only if there is frank papillary muscular rupture; (6) closure of the septal defect without tension, which in most instances will require the use of prosthetic material; (7) closure of the infarctectomy without tension with generous use of prosthetic material as indicated, and epicardial placement of the patch to the free wall to avoid strain on the friable endocardial tissue; and (8) buttressing of the suture lines with pledgets or strips of Teflon felt or similar material to prevent sutures from cutting through friable muscle.

Adult↗
PubMed1998

Evidence for a role of intracellular stored parathyroid hormone in producing hysteresis of the PTH-calcium relationship in normal humans.

OBJECTIVE: Despite the clear recognition that extracellular ionized calcium controls PTH secretion, there have been suggestions of hysteresis in the relationship between extracellular ionized calcium and PTH during recovery from induced hypo- and hypercalcaemia in vivo in humans. In this study, we examined the possibility that release of intracellular stored PTH during induced hypocalcaemia may explain hysteresis. VOLUNTEERS: Eleven volunteers, five women and six men, were recruited to participate in the study. DESIGN: A series of three protocols of repeated induction of hypocalcaemia or sequential induction of hypo- and hypercalcaemia. RESULTS: We observed in a total of 13 trials that a drastic lowering of blood ionized calcium by 0.20 mmol/l within 30 min elicited an immediate large, transient peak release of PTH amounting to 6-16 times the baseline concentration. However, following a steady-state period of hypocalcaemia, a subsequent lowering of blood ionized calcium either following a brief return to normocalcaemia (protocol 1), from the initial hypocalcaemic level of blood ionized calcium (protocol 2) or after a brief period of induced hypercalcaemia (protocol 3) gave either no peak release of PTH or a markedly blunted peak. Thus, the PTH response during the initial induction of and the first recovery from hypocalcaemia in our protocol 3 showed significant hysteresis in the relationship between blood ionized calcium and PTH (P < 0.001), whereas, no hysteretic relationship could be shown during the second recovery from induced hypocalcaemia in four of five cases (NS). Moreover, no hysteretic relationship was observed during induction, recovery and re-induction of hypercalcaemia in protocol 3 (NS). CONCLUSION: We believe that the release of what might be preformed, intracellular stored depot PTH can explain, at least in part, the observed hysteretic PTH-calcium relationship in normal humans.

Adult↗
PubMed1997

Species differences in the expression of major histocompatibility complex class II antigens on coronary artery endothelium: implications for cell-mediated xenoreactivity.

BACKGROUND: There is controversy in the literature as to whether swine coronary endothelium expresses major histocompatibility complex (MHC) class II antigens constitutively. METHODS: Because this issue has implications for cell-mediated human anti-swine xenogeneic responses, we stained tissue sections from human, pig, rat, and mouse hearts with the anti-class II monoclonal antibody ISCR3, which has a similar specificity and titer when binding to human, porcine, and rodent class II molecules. RESULTS: Immunoperoxidase staining of human and porcine hearts with ISCR3 resulted in a dense reaction on the coronary endothelium of epicardial arteries, intramuscular arterioles, and capillaries. In contrast, the coronary endothelium of rat and mouse hearts did not stain with ISCR3. When freshly harvested porcine aortic endothelial cells were placed in culture, class II MHC antigen expression was lost within three to four passages. CONCLUSIONS: Thus, using a single antibody with cross-species reactivities, we demonstrate that swine coronary endothelium, unlike rodent coronary arteries, expresses similar basal amounts of class II MHC antigens to human coronary vessels. The constitutive expression of class II MHC antigens on swine coronary artery endothelium may contribute to host T cell-mediated xenogeneic responses in clinical pig-to-human cardiac xenotransplantation and thus become a target for therapeutic intervention.

Aged↗
PubMed1997

Cardiac operations in patients 80 years old and older.

BACKGROUND: Because the elderly are increasingly referred for operation, we reviewed results with cardiac surgical patients 80 years old or older. METHODS: Records of 600 consecutive patients 80 years old or older having cardiac operations between 1985 and 1995 were reviewed. Follow-up was 99% complete. RESULTS: Two hundred ninety-two patients had coronary grafting (CABG), 105 aortic valve replacement (AVR), 111 AVR + CABG, 42 mitral valve repair/ replacement (MVR) +/- CABG, and 50 other operations. Rates of hospital death, stroke, and prolonged stay (> 14 days) were as follows: CABG: 17 (5.8%), 23 (7.9%) and 91 (31.2%); AVR: 8 (7.6%), 1 (1.0%), and 31 (29.5%); AVR + CABG: 7 (6.3%), 12 (10.8%), and 57 (51.4%); MVR +/- CABG: 4 (9.5%), 3 (7.1%), and 16 (38.1%); other: 9 (18.0%), 3 (6.0%), and 23 (46.0%). Multivariate predictors (p < 0.05) of hospital death were chronic lung disease, postoperative stroke, preoperative intraaortic balloon, and congestive heart failure; predictors of stroke were CABG and carotid disease; and predictors of prolonged stay were postoperative stroke and New York Heart Association class. Actuarial 5-year survival was as follows: CABG, 66%; AVR, 67%; AVR + CABG, 59%; MVR +/- CABG, 57%; other, 48%; and total, 63%. Multivariate predictors of late death were renal insufficiency, postoperative stroke, chronic lung disease, and congestive heart failure. Eighty-seven percent of patients believed having a heart operation after age 80 years was a good choice. CONCLUSIONS: Cardiac operations are successful in most octogenarians with increased hospital mortality, postoperative stroke, and longer hospital stay. Long-term survival is largely determined by concurrent medical diseases.

Actuarial Analysis↗
PubMed1997

Cardiac allograft vasculopathy is abrogated by anti-CD8 monoclonal antibody therapy.

BACKGROUND: Cardiac allograft vasculopathy, a diffuse and accelerated form of arteriosclerosis, is a major cause of graft loss or heart transplant recipient death after the first transplant year. This study examined the effects of depleting host CD8 + T lymphocytes on the development of cardiac allograft vasculopathy in miniature swine. METHODS: Cardiac allografts were heterotopically transplanted across a major histocompatibility complex class I barrier in partially inbred miniature swine and monitored for rejection by serial biopsies, electrocardiograms, and echocardiograms. Four control animals received cyclosporine on postoperative days 0 to 11. Another four miniswine were given 14.5 mg/kg of 76-2-11 (a mouse anti-swine CD8 monoclonal antibody) on postoperative day 0, in addition to a 12-day course of cyclosporine. Host CD8+ T cells and circulating 76-2-11 monoclonal antibodies were monitored by flow cytometry. RESULTS: As compared with cyclosporine-treated control animals, swine receiving 76-2-11 demonstrated near-complete depletion of peripheral CD8+ T cells by postoperative day 2, which persisted for 14 to 18 days. Mean allograft survival of the antibody-treated group and the control group was not statistically different (33 days versus 39 days, respectively) and both groups demonstrated severe interstitial rejection at necropsy. Control animals demonstrated florid intimal thickening of large and small arteries at necropsy. However, swine treated with 76-2-11 showed no intimal proliferation. CONCLUSIONS: Depletion of host CD8+ T cells prevents or delays the development of intimal proliferation in miniature swine. CD8+ lymphocytes play an important role in the early development of cardiac allograft vasculopathy in large animals.

Animals↗
PubMed1996

Composite aortic root replacement with direct coronary artery implantation.

BACKGROUND: Composite aortic root replacement is accepted treatment for aneurysms of the ascending aorta involving the root with aortic valve regurgitation, but controversy continues regarding the best technique of operation. We excise the aneurysm, implant a composite valve graft, directly attach the coronary arteries to the aortic graft, and make the distal anastomosis to the divided aorta. METHODS: We reviewed the records and collected complete follow-up data on 110 consecutive patients having composite aortic root replacement with this technique from 1979 to 1995. RESULTS: Average age was 54 years. Marfan's syndrome was present in 22 patients, acute dissections in 26, chronic dissections in 11, and active endocarditis in 13. Operative characteristics were: 25 emergency procedures, 33 urgent procedures, 52 elective procedures, 24 reoperations, and 19 with coronary artery bypass grafting. Hospital death occurred in 8 patients (7.3%). Multivariate predictors of hospital death were postoperative renal failure and acute dissection. Actuarial survival was 70% at 10 years (standard error, 5%). Multivariate predictors of total mortality were porcine valve, Björk-Shiley valve, preoperative stroke, reoperation on a composite valve graft, and coronary artery bypass grafting. Only 3 patients required late reoperation, all for valve dysfunction. Actuarial freedom from reoperation on the aortic root was 97.3% (standard error, 1.9%) at 10 years. Late echocardiograms in 47 patients showed no anastomotic aneurysms. CONCLUSIONS: Composite aortic root replacement with direct coronary implantation is effective and durable treatment for a variety of aortic pathologic conditions in elective and emergency situations.

Actuarial Analysis↗
PubMed1996

Cardiac allograft vasculopathy in partially inbred miniature swine. I. Time course, pathology, and dependence on immune mechanisms.

To assess the role of the immune system in cardiac allograft vasculopathy in large animals, heterotopic heart transplantation was done between partially inbred miniature swine, animals in which transplantation can be done across defined major histocompatibility barriers in a reproducible fashion. Porcine hearts transplanted into untreated recipients across a class I, class II, or full major histocompatibility mismatch were acutely rejected in 6 to 8 days (n = 4). Hearts transplanted into untreated recipients across minor histocompatibility barriers survived for 21 to 44 days (n = 5) and showed no evidence of cardiac allograft vasculopathy. When recipients were treated with a 12-day course of cyclosporine, hearts transplanted across minor histocompatibility barriers survived 42, 64, and 56 days and did not develop vascular lesions. However, hearts transplanted into cyclosporine-treated recipients across a full major histocompatibility disparity survived 20, 22, and 23 days and all three developed biopsy-proven vasculopathy. In one animal, the progression of intimal proliferation was followed in vivo by intracoronary ultrasonography. The degree of intimal thickening documented by ultrasonography correlated well with the intimal proliferation found on tissue histologic samples. These results are the first to show that in large animals, an immune response stimulated by donor major histocompatibility antigens is involved in the induction of cardiac allograft vasculopathy. In addition, these studies point out the utility of a large-animal model of cardiac allograft vasculopathy in which transplantation across defined major histocompatibility barriers can be done reproducibly and in which accurate determinations of the progression or regression of coronary vascular lesions in individual animals can be accurately assessed in vivo.

Animals↗
PubMed1996

Parathyroid hormone secretion in chronic renal failure.

The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during hemodialysis. During the development of the method we found significantly different results of blood ionized calcium and serum PTH concentration when obtained from the arterial blood line on the dialysis unit or from peripheral venous blood. However, when corrected for the calculated recirculation of 3 to 25%, the result obtained from arterial blood was comparable to the result from venous blood. Furthermore, the results obtained from venous blood were comparable to the results of sequential citrate and calcium clamping performed on a non-dialysis day. From our data of venous blood during hemodialysis, blood PTH/ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure.

Adult↗
PubMed1994

Comparison of backbone dynamics of apo- and holo-acyl-coenzyme A binding protein using 15N relaxation measurements.

15N magnetic relaxation parameters T1, T2 and the nuclear Overhauser effect in the protein acyl-coenzyme A binding protein (ACBP) have been measured in the presence and absence of the ligand, palmitoyl-coenzyme A, in order to obtain information about local and global dynamical properties of the peptide backbone with and without the ligand bound in the binding site. The three-dimensional structures of acyl-coenzyme A binding protein are known for both states of the protein as determined from multidimensional heteronuclear NMR studies, and they have been shown to be essentially identical. However, the dynamics of the backbone is influenced by the presence of ligand in the binding site. The binding of ligand had significant and specific effects on the relaxation time T1 for many of the 15N in the peptide backbone, in particular those near residues with contacts to the ligand. Similarly, the nuclear Overhauser effect at 15N near such residues increased. There were no significant changes in the T2 relaxation. T1 values showing a significant decrease and NOEs increasing in regions close to the binding site when the ligand was bound suggest two modes of action on the dynamics of the protein when the ligand is binding. The reduced T1 indicates motion of lower amplitude in agreement with the structural constraints introduced by protein-ligand interactions. The increased NOEs may be a consequence of shorter time constants for dynamics of the atoms close to the binding site. The Lipari-Szabo model could not be satisfactorily applied to the entire set of experimental data.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1993

Three-dimensional structure of the complex between acyl-coenzyme A binding protein and palmitoyl-coenzyme A.

Multidimensional 1H, 13C and 15N nuclear magnetic resonance spectroscopy has been used to study the complex between palmitoyl-coenzyme A and acyl-coenzyme A binding protein. The 1H and the 15N spectra of the holo-protein have been almost completely assigned and so has most of the 1H spectrum of the coenzyme A part of the protein-bound ligand. The palmitoyl part of the ligand has been uniformly labelled with 13C and the nuclear magnetic resonance signals of the carbon atoms and their protons have been assigned at the two ends of the hydrocarbon chain. A total of 1251 distance restraints from nuclear Overhauser effects and 131 dihedral angle restraints from three-bond coupling constants provided the basis for the structure calculation. A comparison of 20 structures calculated from these data to the average structure showed that they could be aligned with an atomic root-mean-square deviation of 1.3(+/- 0.2) A for all C, N, O, P and S atoms in protein and ligand. The apo-protein is a four-helix protein and this structure is maintained in the holo-protein. The four alpha-helices are Ac1 of residues 3 to 15, Ac2 from residue 20 to 36, Ac3 from 51 to 62, and Ac4 from 65 to 84. For the four alpha-helices of the peptide backbone of the holo-protein the root-mean-square deviation for the C, C alpha and N atoms was 0.42(+/- 0.08) A. The binding site for the palmitoyl-chain stretches between the N-terminal end of Ac3 where the carboxyl part binds, to the N-terminal of Ac3 where the omega-end of the palmitoyl part binds. The adenosine-3'-phosphate is bound near residues of each of the four helices in an arrangement where it can form salt bridges and/or hydrogen bonds to either backbone or side-chain atoms of Ala9, Tyr28, Lys32, Lys54 and Tyr73. The polar parts of the pantetheine and the pyrophosphate are structured in the bound ligand to form an interface with the solvent. Also the ligand forms a set of non-polar intramolecular interactions where the adenine, the pantetheine, and the palmitoyl-chain are associated, so overall the structure of the bound ligand seems to be organized to protect the lipophilic palmitoyl part from the polar solvent.

Amino Acid Sequence↗