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Biomedical subjects

T A Jones

Publications and source records attributed to T A Jones.

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

Denervation facilitates neuronal growth in the motor cortex of rats in the presence of behavioral demand.

This study tests the hypothesis that degeneration of a neocortical pathway may facilitate behaviorally-induced growth of neurons in a connected region of the cortex. Degeneration of trancallosal afferents to the motor cortex and changes in forelimb use were independently manipulated in adult rats. The combination of degeneration and behavioral change resulted in the growth of layer V pyramidal neuron dendrites which was not found as a result of either denervation or behavioral manipulation alone. These results indicate that mild degeneration in the adult brain can facilitate neuronal growth when accompanied by appropriate behavioral demand, a finding which has implications for rehabilitative therapy after brain damage.

Animals↗
PubMed2000

Reactive astrocytic responses to denervation in the motor cortex of adult rats are sensitive to manipulations of behavioral experience.

Recent research has suggested that mild denervation of the neocortex of adult rats may facilitate neuronal growth in response to behavioral changes. Astrocytes react to denervation, produce growth-promoting factors and are a potential mediator of this denervation-facilitated growth. The present study assessed whether astrocytic reactions to denervation vary dependent upon post-injury behavioral experience. Denervation of the transcallosal afferents to the motor cortex was induced via partial transections of the corpus callosum. Transected- or sham-operated rats were then either forced to use the opposite forelimb (via limb-restricting vests) or permitted to use both forelimbs normally for 8 days. In the motor cortex, the surface density of glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytic processes and the density of basic fibroblast growth factor (FGF-2)-IR glial cells was significantly increased as a result of transections alone and as a result of forced forelimb-use alone in comparison to controls. The combination of transections and forced-use significantly enhanced GFAP-IR in comparison to all other groups, but did not further enhance FGF-2-IR. These findings are consistent with behavior and denervation having interactive influences on astrocytic reactivity in the motor cortex. These results also raise the possibility that astrocyte-mediated support of neural restructuring after brain injury might be enhanced with appropriate post-injury behavioral manipulations.

Animals↗
PubMed2000

Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases.

BACKGROUND: Epoxide hydrolases have important roles in the defense of cells against potentially harmful epoxides. Conversion of epoxides into less toxic and more easily excreted diols is a universally successful strategy. A number of microorganisms employ the same chemistry to process epoxides for use as carbon sources. RESULTS: The X-ray structure of the epoxide hydrolase from Aspergillus niger was determined at 3.5 A resolution using the multiwavelength anomalous dispersion (MAD) method, and then refined at 1.8 A resolution. There is a dimer consisting of two 44 kDa subunits in the asymmetric unit. Each subunit consists of an alpha/beta hydrolase fold, and a primarily helical lid over the active site. The dimer interface includes lid-lid interactions as well as contributions from an N-terminal meander. The active site contains a classical catalytic triad, and two tyrosines and a glutamic acid residue that are likely to assist in catalysis. CONCLUSIONS: The Aspergillus enzyme provides the first structure of an epoxide hydrolase with strong relationships to the most important enzyme of human epoxide metabolism, the microsomal epoxide hydrolase. Differences in active-site residues, especially in components that assist in epoxide ring opening and hydrolysis of the enzyme-substrate intermediate, might explain why the fungal enzyme attains the greater speeds necessary for an effective metabolic enzyme. The N-terminal domain that is characteristic of microsomal epoxide hydrolases corresponds to a meander that is critical for dimer formation in the Aspergillus enzyme.

Animals↗
PubMed2000

Experience-dependent structural plasticity in cortex heterotopic to focal sensorimotor cortical damage.

Structural plasticity following focal neocortical damage in adult rats has recently been found to be sensitive to postinjury rehabilitative training. Experience on a complex motor skills task, the acrobatic task, after unilateral lesions of the forelimb representation region of the sensorimotor cortex (FLsmc) enhanced synaptic structural changes in the cortex contralateral and homotopic to the lesions. Using tissue from this previous study, the present study examined whether a heterotopic region of the sensorimotor cortex of either hemisphere, the hindlimb representation area (HLsmc), would undergo structural changes following unilateral FLsmc lesions and whether these changes would also be sensitive to postinjury training on the acrobatic task. Stereological methods for light and electron microscopy were used to assess structural changes in lesion or sham-operated rats following 28 days of postoperative acrobatic training or simple repetitive exercise (motor controls). In the HLsmc contralateral to the lesions of rats receiving acrobatic training, there was a subtle, but significant, increase in cortical volume and in layer II/III neuropil and dendritic volume per neuron in comparison to shams. In rats receiving simple exercise after the lesions, these changes were not significantly different from shams. Acrobatic training also prevented a loss of cortical volume in the HLsmc adjacent to the lesion in comparison to shams. These data suggest that behavioral training following cortical injury facilitates structural plasticity in behaviorally relevant areas of the neocortex other than the homotopic cortex contralateral to the lesion. This structural plasticity might be relevant to the development of behavioral compensation after cortical injury.

Animals↗
PubMed2000

Ontogeny of vestibular compound action potentials in the domestic chicken.

Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

Action Potentials↗
PubMed2000

The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines.

Neuroblastoma is a childhood tumour of the sympathetic nervous system that demonstrates striking clinical heterogeneity. In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (MEIS1), is highly amplified. MEIS1 normally maps to chromosome band 2p14. High expression of MEIS1 without amplification was also found in other neuroblastoma cell lines, with and without MYCN amplification, and in medulloblastoma and crythroleukaemia cell lines. MEIS1 is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.

Blotting, Northern↗
PubMed2000

Assessment of the cosmic radiation exposure on Canadian-based routes.

As a result of the recent recommendations of the ICRP-60 and in anticipation of possible regulation on occupational exposure of commercial aircrew, a two-phase investigation was carried out over a 1-y period to determine the total dose equivalent on representative Canadian-based flight routes. In the first phase of the study, dedicated scientific flights on a Northern round-trip route between Ottawa and Resolute Bay provided the opportunity to characterize the complex mixed-radiation field and to intercompare various instrumentation using both a conventional suite of powered detectors and passive dosimetry. In the second phase, volunteer aircrew carried (passive) neutron bubble detectors during their routine flight duties. From these measurements, the total dose equivalent was derived for a given route with a knowledge of the neutron fraction as determined from the scientific flights and computer code (CARI-3C) calculations. This study has yielded an extensive database of over 3,100 measurements providing the total dose equivalent for 385 different routes. By folding in flight frequency information and the accumulated flight hours, the annual occupational exposures of 20 flight crew have been determined. This study has indicated that most Canadian-based domestic and international aircrew will exceed the proposed annual ICRP-60 public limit of 1 mSv y(-1) but will be well below the occupational limit of 20 mSv y(-1).

Aircraft↗
PubMed2000

Spontaneous activity in the statoacoustic ganglion of the chicken embryo.

Statoacoustic ganglion cells in the mature bird include neurons that are responsive to sound (auditory) and those that are not (nonauditory). Those that are nonauditory have been shown to innervate an otolith organ, the macula lagena, whereas auditory neurons innervate the basilar papilla. In the present study, single-unit recordings of statoacoustic ganglion cells were made in embryonic (E19, mean = 19.2 days of incubation) and hatchling (P6-P14, mean = 8.6 days posthatch) chickens. Spontaneous activity from the two age groups was compared with developmental changes. Activity was evaluated for 47 auditory, 11 nonauditory, and 6 undefined eighth nerve neurons in embryos and 29 auditory, 26 nonauditory, and 1 undefined neurons in hatchlings. For auditory neurons, spontaneous activity displayed an irregular pattern [discharge interval coefficient of variation (CV) was >0.5, mean CV for embryos was 1.46 +/- 0.58 and for hatchlings was 1.02 +/- 0.25; means +/- SD]. Embryonic discharge rates ranged from 0.05 to 97.6 spikes per second (sp/s) for all neurons (mean 18.6 +/- 16.9 sp/s). Hatchling spontaneous rates ranged from 1.2 to 185.2 sp/s (mean 66.5 +/- 39.6 sp/s). Discharge rates were significantly higher for hatchlings (P < 0.001). Many embryonic auditory neurons displayed long silent periods between irregular bursts of neural activity, a feature not seen posthatch. All regular bursting discharge patterns were correlated with heart rate in both embryos and hatchlings. Preferred intervals were visible in the time interval histograms (TIHs) of only one embryonic neuron in contrast to 55% of the neurons in posthatch animals. Generally, the embryonic auditory TIH displayed a modified quasi-Poisson distribution. Nonauditory units generally displayed regular (CV <0.5) or irregular (CV >0.5) activity and Gaussian and modified-Gaussian TIHs. Long silent periods or bursting patterns were not a characteristic of embryonic nonauditory neurons. CV varied systematically as a function of discharge rate in nonauditory but not auditory primary afferents. Minimum spike intervals (dead time) and interval modes for auditory neurons were longer in embryos (dead time: embryos 2.88 +/- 6.85 ms; hatchlings 1.50 +/- 1.76 ms; modal intervals: embryo 10.09 +/- 22.50 ms, hatchling 3.54 +/- 3.29 ms). The results show that significant developmental changes occur in spontaneous activity between E19 and posthatch. It is likely that both presynaptic and postsynaptic changes in the neuroepithelium contribute to maturational refinements during this period of development.

Acoustic Stimulation↗
PubMed2000

Narrowing of the region of allelic loss in 21q11-21 in squamous non-small cell lung carcinoma and cloning of a novel ubiquitin-specific protease gene from the deleted segment.

We examined 42 fresh non-small cell lung carcinomas for allelic loss using 4 microsatellite markers located in a 4.5 Mb region in 21q11-21, a gene-poor interval recently found by others to be homozygously deleted and exhibiting frequent allelic loss in lung cancer. We found allelic loss across the entire segment in 13/34 informative squamous carcinomas, with 2 cases showing loss in only part of the region. Analysis by fluorescence in situ hybridization of P1-derived artificial chromosomes from the region directly on paraffin sections of the tumor is in concordance with the loss of heterozygosity (LOH) results, and tentatively excludes a 2 Mb segment bearing 2 of the only 3 known genes in the area. Exon trapping in the remaining segment of loss led to identification and cloning of a novel gene spanning 150 kb within the deletion. The full-length gene encodes a protein of 1,055 amino acids with homology to ubiquitin-specific proteases across the eukaryotic evolutionary spectrum. The expressed protein acts as a de-ubiquitinating enzyme as proved by the ability to cleave ubiquitin from a model fusion protein. We found no mutations in the sequence of the functional domains of this gene in any of the LOH-exhibiting tumor DNA samples. It is, however, interesting that genes of the same superfamily have been reported on 3p21, a locus showing the most frequent allelic instability and deletions in lung cancer. Genes Chromosomes Cancer 27:153-161, 2000.

Amino Acid Sequence↗
PubMed2000

Ubiquity of the St chloroplast genome in St-containing Triticeae polyploids.

Interspecific hybridization occurs between Tritceae species in the grass family (Poaceae) giving rise to allopolyploid species. To examine bias in cytoplasmic DNA inheritance in these hybridizations, the sequence of the 3' end of the chloroplast ndhF gene was compared among 29 allopolyploid Triticeae species containing the St nuclear genome in combination with the H, I, Ns, P, W, Y, and Xm nuclear genomes. These ndhF sequences were also compared with those from diploid or allotetraploid Triticeae species having the H, I, Ns, P, W, St, and Xm genomes. The cpDNA sequences were highly similar among diploid, allotetraploid, allohexaploid, and allooctoploid Triticeae accessions containing the St nuclear genome, with 0-6-nucleotide (nt) substitutions (0-0.8%) occurring between pairs of species. Neighbor-joining analysis of the sequences showed that the ndhF DNA sequences from species containing the St nuclear genome formed a strongly supported clade. The data indicated a strong preference for cpDNA inheritance from the St nuclear genome-containing parent in hybridizations between Triticeae species. This preference was independent of the presence of the H, I, Ns, P, W, and Xm nuclear genomes, the geographic distribution of the species, and the mode of reproduction. The data suggests that hybridizations having the St-containing parent as the female may be more successful.

Chloroplasts↗
PubMed2000

Modification of immunologic and hematologic variables by method of CO2 euthanasia.

BACKGROUND AND PURPOSE: The major goal was to determine whether variations in the method of CO2 euthanasia would induce significant immunologic differences. METHODS: Young adult C57BL/6 mice (n = 40) were euthanized, using four regimens: 70% CO2/30% O2; 70% CO2/30% O2-->100% CO2; 100% CO2-naïve chamber; and 100% CO2 pre-charged chamber. Time to recumbency and euthanasia and body, liver, lung, spleen, and thymus masses were determined. Blood and spleen were further evaluated for leukocyte, lymphocyte, and thrombocyte counts, erythrocyte characteristics, distribution of lymphocyte subpopulations, spontaneous and mitogen-induced blastogenesis, complement activity, and cytokine production. RESULTS: Time to euthanasia was five- to eightfold longer in mice exposed to 70% CO2/30% O2 than that for any other group. There were slight increases in mean erythrocyte volume (MCV) and mean erythrocyte hemoglobin (MCH) for all groups, compared with those for the 100% CO2 pre-charged group. Circulating cytotoxic T (CD8+) lymphocyte percentages and numbers, and spontaneous blastogenesis of leukocytes in blood and spleen, also were affected by euthanasia method. CONCLUSIONS: The method of CO2 euthanasia can result in significant differences in immunologic/hematologic variables. Thus, consistency in euthanasia procedures may be important in accurate interpretation of research data.

Animals↗
PubMed2000

The effects of hypergravity and substrate vibration on vestibular function in developing chickens.

We used linear vestibular evoked potentials (VsEPs) to characterize peripheral and central vestibular function in birds following embryogenesis at 2G centrifugation or at elevated levels of vibration (+20dB re: background levels). Additionally, we characterized peripheral and central vestibular adaptation to 2G centrifugation in early post-hatch birds. Linear VsEP response peak latencies, amplitudes, thresholds and input/output functions were quantified and compared between experimental and control animals. Birds vibrated throughout embryogenesis and up to one-week post-hatch revealed no changes in linear VsEP response components compared to control siblings. Birds centrifuged at 2G throughout embryogenesis also evidenced no changes in the linear VsEP measured at hatch (P0). Significant changes were seen, however, for linear VsEPs of post-hatch birds placed at 2G for 7 days beginning on post-hatch day 5. Linear VsEPs for these animals displayed significant reductions in response amplitudes associated with peaks P2, N2 and P3, response peaks generated by central neural relays of gravity receptors. The earliest response components, generated by the peripheral vestibular nerve (i.e., P1, N1), were not significantly altered with the 7-day exposure to 2G. Thus, there was no evidence of generalized changes in peripheral gravity receptor excitability or in the rate of maturation in developing animals under increased levels of gravity or vibration. If gravity level plays a critical role in shaping peripheral vestibular ontogeny at magnitudes between 1 and 2G, then it may serve to stabilize function under changing G-fields or it may operate on physiological features that can not be resolved by the VsEP. In contrast, exposure to elevated gravity during post-hatch periods does alter central vestibular function thus providing direct evidence for central vestibular adaptation to the gravitational environment. The fact that central functional change was observed in hatchlings and not embryos, raises the possibility that the first 2-weeks post-hatch may be a critical period of "heightened developmental sensitivity" to hypergravity.

Adaptation, Physiological↗
PubMed1999

Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A).

Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homolog in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and protein interactions of SV2 suggest multiple possible functions, its role in synaptic events remains unknown. To explore the function of SV2 in an in vivo context, we generated mice that do not express the primary SV2 isoform, SV2A, by using targeted gene disruption. Animals homozygous for the SV2A gene disruption appear normal at birth. However, they fail to grow, experience severe seizures, and die within 3 weeks, suggesting multiple neural and endocrine deficits. Electrophysiological studies of spontaneous inhibitory neurotransmission in the CA3 region of the hippocampus revealed that loss of SV2A leads to a reduction in action potential-dependent gamma-aminobutyric acid (GABA)ergic neurotransmission. In contrast, action potential-independent neurotransmission was normal. Analyses of synapse ultrastructure suggest that altered neurotransmission is not caused by changes in synapse density or morphology. These findings demonstrate that SV2A is an essential protein and implicate it in the control of exocytosis.

Animals↗
PubMed1999

Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats.

To assess behavioral experience effects on synaptic plasticity after brain damage, the present study examined the effects of complex motor skills training (the acrobatic task) on synaptic changes in layer V of the motor cortex opposite unilateral damage to the forelimb sensorimotor cortex (FLsmc). Adult male rats were given lesions or sham operations followed by 28 d of training on the acrobatic task [acrobat condition (AC)]. As a motor activity control [motor control (MC)], lesion and sham animals were given simple repetitive exercise. Previously, FLsmc lesions and acrobatic training have independently been found to result in increases in synapse to neuron ratios in the intact motor cortex relative to controls, and both of these effects were replicated in the present study. In addition, acrobat training after lesions significantly increased layer V synapses per neuron relative to sham-AC and lesion-MC rats. Thus, the combination of acrobatic training and lesions resulted in an enhanced synaptogenic response. Synapse subtypes were also differentially affected by the conditions. Lesion-MC and sham-AC primarily had increases in the number of synapses per neuron formed by multiple synaptic boutons in comparison to sham-MC. In contrast, lesion-AC had increases in both multiple and single synapses. Multiple synaptic spines and perforated synapses were also differentially affected by training versus lesions. On tests of coordinated forelimb use, lesion-AC rats performed better than lesion-MC rats. In addition to supporting a link between behavioral experience and structural plasticity after brain damage, these findings suggest that adaptive neural plasticity may be enhanced using behavioral manipulations as "therapy."

Animals↗
PubMed1999

Multiple synapse formation in the motor cortex opposite unilateral sensorimotor cortex lesions in adult rats.

Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) in adult rats has previously been found to result in dendritic growth and synaptogenesis in layer V of the contralateral motor cortex. The neuronal growth appears to be mediated in part by lesion-induced changes in the use of the forelimbs. Whether these neuronal changes involve alterations in the structure and/or configuration of synaptic connections in layer V has not previously been investigated. The present study used stereological measures to characterize structural alterations in axonal processes and synaptic connections using electron micrographs generated in a previous study of the motor cortex contralateral to FLsmc lesions. Of primary interest were synapses formed by multiple synaptic boutons (MSBs), which have recently been found to be a major component of experience-related neocortical plasticity, and synapses with perforated postsynaptic densities (PSDs), which are putatively associated with enhanced synaptic efficacy. In comparison with sham-operated rats, there was an increase in the proportion and ratio of synapses to neurons formed by MSBs and in synapses with perforated PSDs at 30 days after the lesions. Furthermore, perforated synapses formed by MSBs were markedly increased at 18 and 30 days after the lesion in comparison with sham-operated rats. Preceding these synaptic structural changes (at 10 days postlesion), myelinated axons were reduced in volume fraction and volume per neuron in comparison with sham-operated rats but returned to normal levels at subsequent time points. These results are consistent with a lesion-induced degeneration and subsequent sprouting of axons. Together, these data indicate that a major restructuring of synaptic connectivity occurs in the cortex opposite FLsmc lesions in adult animals. This lesion-induced restructuring may be guided by ongoing changes in the use of the forelimbs.

Animals↗
PubMed1999

Crystallographic evidence for substrate ring distortion and protein conformational changes during catalysis in cellobiohydrolase Ce16A from trichoderma reesei.

BACKGROUND: Cel6A is one of the two cellobiohydrolases produced by Trichoderma reesei. The catalytic core has a structure that is a variation of the classic TIM barrel. The active site is located inside a tunnel, the roof of which is formed mainly by a pair of loops. RESULTS: We describe three new ligand complexes. One is the structure of the wild-type enzyme in complex with a nonhydrolysable cello-oligosaccharide, methyl 4-S-beta-cellobiosyl-4-thio-beta-cellobioside (Glc)(2)-S-(Glc)(2), which differs from a cellotetraose in the nature of the central glycosidic linkage where a sulphur atom replaces an oxygen atom. The second structure is a mutant, Y169F, in complex with the same ligand, and the third is the wild-type enzyme in complex with m-iodobenzyl beta-D-glucopyranosyl-beta(1,4)-D-xylopyranoside (IBXG). CONCLUSIONS: The (Glc)(2)-S-(Glc)(2) ligand binds in the -2 to +2 sites in both the wild-type and mutant enzymes. The glucosyl unit in the -1 site is distorted from the usual chair conformation in both structures. The IBXG ligand binds in the -2 to +1 sites, with the xylosyl unit in the -1 site where it adopts the energetically favourable chair conformation. The -1 site glucosyl of the (Glc)(2)-S-(Glc)(2) ligand is unable to take on this conformation because of steric clashes with the protein. The crystallographic results show that one of the tunnel-forming loops in Cel6A is sensitive to modifications at the active site, and is able to take on a number of different conformations. One of the conformational changes disrupts a set of interactions at the active site that we propose is an integral part of the reaction mechanism.

Binding Sites↗
PubMed1999

Structure of D-allose binding protein from Escherichia coli bound to D-allose at 1.8 A resolution.

ABC transport systems for import or export of nutrients and other substances across the cell membrane are widely distributed in nature. In most bacterial systems, a periplasmic component is the primary determinant of specificity of the transport complex as a whole. We report here the crystal structure of the periplasmic binding protein for the allose system (ALBP) from Escherichia coli, solved at 1.8 A resolution using the molecular replacement method. As in the other members of the family (especially the ribose binding protein, RBP, with which it shares 35 % sequence homology), this structure consists of two similar domains joined by a three-stranded hinge region. The protein is believed to exist in a dynamic equilibrium of closed and open conformations in solution which is an important part of its function. In the closed ligand-bound form observed here, D-allose is buried at the domain interface. Only the beta-anomer of allopyranose is seen in the crystal structure, although the alpha-anomer can potentially bind with a similar affinity. Details of the ligand-binding cleft reveal the features that determine substrate specificity. Extensive hydrogen bonding as well as hydrophobic interactions are found to be important. Altogether ten residues from both the domains form 14 hydrogen bonds with the sugar. In addition, three aromatic rings, one from each domain with faces parallel to the plane of the sugar ring and a third perpendicular, make up a hydrophobic stacking surface for the ring hydrogen atoms. Our results indicate that the aromatic rings forming the sugar binding cleft can sterically block the binding of any hexose epimer except D-allose, 6-deoxy-allose or 3-deoxy-glucose; the latter two are expected to bind with reduced affinity, due to the loss of some hydrogen bonds. The pyranose form of the pentose, D-ribose, can also fit into the ALBP binding cleft, although with lower binding affinity. Thus, ALBP can function as a low affinity transporter for D-ribose. The significance of these results is discussed in the context of the function of allose and ribose transport systems.

ATP-Binding Cassette Transporters↗