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H Li

Publications and source records attributed to H Li.

At least 469 records · Page 26Linked to original sources
PubMed2000

Structure of the FHA1 domain of yeast Rad53 and identification of binding sites for both FHA1 and its target protein Rad9.

Forkhead-associated (FHA) domains have been shown to recognize both pThr and pTyr-peptides. The solution structures of the FHA2 domain of Rad53 from Saccharomyces cerevisiae, and its complex with a pTyr peptide, have been reported recently. We now report the solution structure of the other FHA domain of Rad53, FHA1 (residues 14-164), and identification of binding sites of FHA1 and its target protein Rad9. The FHA1 structure consists of 11 beta-strands, which form two large twisted anti-parallel beta-sheets folding into a beta-sandwich. Three short alpha-helices were also identified. The beta-strands are linked by several loops and turns. These structural features of free FHA1 are similar to those of free FHA2, but there are significant differences in the loops. Screening of a peptide library [XXX(pT)XXX] against FHA1 revealed an absolute requirement for Asp at the +3 position and a preference for Ala at the +2 position. These two criteria are met by a pThr motif (192)TEAD(195) in Rad9. Surface plasmon resonance analysis showed that a pThr peptide containing this motif, (188)SLEV(pT)EADATFVQ(200) from Rad9, binds to FHA1 with a K(d) value of 0.36 microM. Other peptides containing pTXXD sequences also bound to FHA1, but less tightly (K(d)=4-70 microM). These results suggest that Thr192 of Rad9 is the likely phosphorylation site recognized by the FHA1 domain of Rad53. The tight-binding peptide was then used to identify residues of FHA1 involved in the interaction with the pThr peptide. The results are compared with the interactions between the FHA2 domain and a pTyr peptide derived from Rad9 reported previously.

Amino Acid Motifs↗
PubMed2000

Further definition of the substance P (SP)/neurokinin-1 receptor complex. MET-174 is the site of photoinsertion p-benzoylphenylalanine4 SP.

The covalent attachment site of a substance P (SP) analogue containing the photoreactive amino acid p-benzoyl-l-phenylalanine (Bpa) in position 8 of the C-terminal portion of the peptide was identified previously as Met-181 on the neurokinin-1 (NK-1) receptor. In this study, a second photoreactive SP analogue, Bpa(4)-SP, in which the Bpa residue is located in the N-terminal portion of the peptide, was used to define further the peptide-receptor interface. The NK-1 receptor expressed in Chinese hamster ovary cells was specifically and efficiently photolabeled with a radioiodinated derivative of Bpa(4)-SP. Fragmentation analysis of the photolabeled receptor restricted the site of photoincorporation of Bpa(4)-SP to an amino acid within the sequence Thr-173 to Arg-177 located on the N-terminal side of the E2 loop. To identify the specific amino acid in this sequence that serves as the covalent attachment site for Bpa(4)-SP, a small photolabeled receptor fragment was generated by chemical cleavage with cyanogen bromide. Matrix-assisted laser desorption/ionization time of flight mass spectrometric analysis of the purified fragment identified a single protonated molecular ion with a molecular mass of 1801.3 +/- 1.8, indicating that upon irradiation, the bound photoligand covalently attaches to the terminal methyl group of a methionine residue. This result, taken together with the results of the peptide mapping studies, establishes that the site of Bpa(4)-SP covalent attachment to the NK-1 receptor is Met-174.

Animals↗
PubMed2000

Glucosamine inhibits inducible nitric oxide synthesis.

Glucosamine is widely used in Europe for treatment of arthritis in humans. Based on recent findings that excess production of nitric oxide (NO) by inducible NO synthase (iNOS) mediates the pathogenesis of arthritis, we hypothesized that glucosamine may inhibit NO synthesis. To test this hypothesis, we used an in vivo rat model of lipopolysaccharide (LPS)-induced inflammation. Intravenous administration of d-glucosamine (0.5 mmol/kg) 6 h before, at the time of, and 6 h after intraperitoneal LPS injection (1 mg/kg) decreased urinary excretion of nitrate by 31 and 48%, respectively, at days 1 and 2 post LPS administration. When cultured macrophages were treated with LPS (1 microg/ml) to induce iNOS expression, addition of 0.1, 0.5, 1, and 2 mM d-glucosamine decreased NO production by 18, 38, 60, and 89%, respectively. Glucosamine had no effect on cellular arginine, NADPH or tetrahydrobiopterin concentrations, but dose-dependently suppressed iNOS protein expression. Similar decreases in iNOS protein occurred in spleen, lung, and peritoneal macrophages of glucosamine-treated rats. These studies demonstrate that glucosamine is a novel inhibitor of inducible NO synthesis via inhibition of iNOS protein expression, and provide a biochemical basis for the use of glucosamine in treating chronic inflammatory diseases such as arthritis.

Animals↗
PubMed2000

Vancomycin-resistant enterococci among chronic hemodialysis patients: a prospective study of acquisition.

To determine the prevalence and rate of acquisition of vancomycin-resistant enterococci (VRE) among patients undergoing chronic (i.e., long-term) hemodialysis who were admitted to a tertiary care center, serial rectal cultures for VRE were performed at hospital admission and every 5 days until hospital discharge. A total of 7 (6%) of the 119 patients were colonized with VRE at admission. Six (19%) of the 32 patients who remained in the hospital > or =4 days acquired VRE. A nonambulatory status was significantly associated with colonization at admission (OR, 9.7; 95% CI, 1.8-53; P=.01), and vancomycin exposure was significantly associated with VRE acquisition (relative risk, 1.8; 95% CI, 1.1-2.9; P=.02). All patients acquired VRE from epidemiologically linked dialysis patients colonized with similar VRE genotypes. Hospital acquisition of VRE contributes substantially to the increasing prevalence of VRE in the chronic hemodialysis patient population.

Adult↗
PubMed2000

Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma.

Several bismuth compounds are currently used as antiulcer drugs, but their mechanism of action is not well established. Proteins are thought to be target sites. In this work we establish that the competitive binding of Bi(3+) to the blood serum proteins albumin and transferrin, as isolated proteins and in blood plasma, can be monitored via observation of (1)H and (13)C NMR resonances of isotopically labeled [epsilon-(13)C]Met transferrin. We show that Met(132) in the I132M recombinant N-lobe transferrin mutant is a sensitive indicator of N-lobe metal binding. Bi(3+) binds to the specific Fe(3+) sites of transferrin and the observed shifts of Met resonances suggest that Bi(3+) induces similar conformational changes in the N-lobe of transferrin in aqueous solution and plasma. Bi(3+) binding to albumin is nonspecific and Cys(34) is not a major binding site, which is surprising because Bi(3+) has a high affinity for thiolate sulfur. This illustrates that the potential target sites for metals (in this case Bi(3+)) in proteins depend not only on their presence but also on their accessibility. Bi(3+) binds to transferrin in preference to albumin both in aqueous solution and in blood plasma.

Albumins↗
PubMed2000

Vertebral blood flow and bone mineral density during long-term corticosteroid treatment: An experimental study in immature pigs.

STUDY DESIGN: Bone mineral density and regional blood flow were measured in pigs during long-term methylprednisolone treatment. OBJECTIVES: To investigate possible changes in bone mineral density and vertebral blood flow during long-term glucocorticoid treatment. SUMMARY OF BACKGROUND DATA: Steroid-induced vertebral osteonecrosis preferentially involves endplates and adjacent cancellous bone. The precise etiology of vertebral osteonecrosis during long-term glucocorticoid treatment is unknown. METHODS: Twenty-four 10-week-old female Danish landrace sister pigs from 12 litters were treated in two groups. Twelve animals received oral methylprednisolone for 3 months at a daily dose of 100 mg. The 12 sister pigs received no steroid treatment and served as controls. Regional blood blow was measured by means of microspheres in predefined regions of the C6, T11, and L6 vertebrae. In vitro DEXA scanning of the L2-L4 vertebra was performed to assess bone mineral density. RESULTS: Vertebral cancellous bone and endplate regional blood flow were decreased in the C6 and L6 vertebrae among corticosteroid-treated pigs compared with that of controls.- Width-adjusted lumbar vertebral bone mineral density (g/cm3) was unchanged, whereas projectional lumbar vertebral bone mineral density (g/cm2) was decreased in corticosteroid-treated pigs. CONCLUSIONS: Long-term methylprednisolone treatment decreases vertebral bone blood flow mainly in cancellous bone and endplates. This may be an important factor in the pathogenesis of osteonecrosis secondary to glucocorticoid treatment. Lumbar vertebral bone mineral density was unchanged in growing pigs on long-term glucocorticoid treatment when expressed as volumetric bone density. The effect of glucocorticoid treatment on vertebral bone mineral density appears to depend on whether it is expressed as projectional (g/cm2) or volumetric bone mineral density (g/cm3). Vertebral and longbone growth was reduced during methylprednisolone treatment.

Animals↗
PubMed2000

Molecular diversity of the repolarizing voltage-gated K+ currents in mouse atrial cells.

Voltage-clamp studies on atrial myocytes isolated from adult and postnatal day 15 (P15) C57BL6 mice demonstrate the presence of three kinetically distinct Ca2+-independent, depolarization-activated outward K+ currents: a fast, transient outward current (Ito,f), a rapidly activating, slowly inactivating current (IK,s) and a non-inactivating, steady-state current (Iss). The time- and voltage-dependent properties of to,f, IK,s and Iss in adult and P15 atrial cells are indistinguishable. Pharmacological experiments reveal the presence of two components of IK,s: one that is blocked selectively by 50 microM 4-aminopyridine (4-AP), and a 4-AP-insensitive component that is blocked by 25 mM TEA; Iss is also partially attenuated by 25 mM TEA. There are also two components of IK,s recovery from steady-state inactivation. To explore the molecular correlates of mouse atrial IK,s and Iss, whole-cell voltage-clamp recordings were obtained from P15 and adult atrial cells isolated from transgenic mice expressing a mutant Kv2.1 alpha subunit (Kv2.1N216Flag) that functions as a dominant negative, and from P15 atrial myocytes exposed to (1 microM) antisense oligodeoxynucleotides (AsODNs) targeted against Kv1.5 or Kv2.1. Peak outward K+ current densities are attenuated significantly in atrial myocytes isolated from P15 and adult Kv2.1N216Flag-expressing animals and in P15 cells exposed to AsODNs targeted against either Kv1.5 or Kv2.1. Analysis of the decay phases of the outward currents evoked during long (5 s) depolarizing voltage steps revealed that IK, s is selectively attenuated in cells exposed to the Kv1.5 AsODN, whereas both IK,s and Iss are attenuated in the presence of the Kv2. 1 AsODN. In P15 and adult Kv2.1N216Flag-expressing atrial cells, mean +/- s.e.m. IK,s and Iss densities are also significantly lower than in non-transgenic atrial cells. In addition, pharmacological experiments reveal that the TEA-sensitive component IK,s is selectively eliminated in P15 and adult Kv2.1N216Flag-expressing atrial cells. Taken together, the results presented here reveal that both Kv1.5 and Kv2.1 contribute to mouse atrial IK,s, consistent with the presence of two molecularly distinct components of IK,s. In addition, Kv2.1 contributes to mouse atrial Iss.

4-Aminopyridine↗
PubMed2000

Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosis.

Thromboxane A(2) is a potent vasoconstrictor and platelet agonist; prostacyclin is a potent platelet inhibitor and vasodilator. Altered biosynthesis of these eicosanoids is a feature of human hypercholesterolemia and atherosclerosis. This study examined whether in 2 murine models of atherosclerosis their levels are increased and correlated with the evolution of the disease. Urinary 2,3-dinor thromboxane B(2) and 2,3-dinor-6-keto prostaglandin F(1 alpha), metabolites of thromboxane and prostacyclin, respectively, were assayed in apoliprotein E (apoE)-deficient mice on chow and low-density lipoprotein receptor (LDLR)-deficient mice on chow and a Western-type diet. Atherosclerosis lesion area was measured by en face method. Both eicosanoids increased in apoE-deficient mice on chow and in LDLR-deficient mice on a high-fat diet, but not in LDLR-deficient mice on chow by the end of the study. Aspirin suppressed ex vivo platelet aggregation, serum thromboxane B(2), and 2,3-dinor thromboxane B(2), and significantly reduced the excretion of 2,3-dinor-6-keto prostaglandin F(1 alpha) in these animals. This study demonstrates that thromboxane as well as prostacyclin biosynthesis is increased in 2 murine models of atherogenesis and is secondary to increased in vivo platelet activation. Assessment of their generation in these models may afford the basis for future studies on the functional role of these eicosanoids in the evolution and progression of atherosclerosis. (Blood. 2000;96:3823-3826)

Age Factors↗
PubMed2000

Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones.

The HIV-1 Tat protein is required for viral replication and is a potent stimulator of viral transcription. Although Tat has been extensively studied in various reductive paradigms, to date there is little information as to how this activator mediates transcription from natural nucleosomally packaged long terminal repeats. Here we show that CREB-binding protein (CBP)/p300 interacts with the HIV-1 Tat protein and serves as a coactivator of Tat-dependent HIV-1 gene expression on an integrated HIV-1 provirus. The site of acetylation of Tat was mapped to the double-lysine motif in a highly conserved region, (49)RKKRRQ(54), of the basic RNA-binding motif of Tat. Using HLM1 cells (HIV-1(+)/Tat(-)), which contain a single copy of full-length HIV-1 provirus with a triple termination codon at the first AUG of the Tat gene, we find that only wild type, and not K50A, K51A, or K50A/K51A alone or in combination of ectopic CBP/p300, is able to produce full-length infectious virions, as measured by p24 gag ELISAs. Tat binds CBP/p300 in the minimal histone acetyltransferase domain (1253-1710) and the binding is stable up to 0.85 M salt wash conditions. Interestingly, wild-type peptide 41-54, and not other Tat peptides, changes the conformation of the CBP/p300 such that it can acquire and bind better to basal factors such as TBP and TFIIB, indicating that Tat may influence the transcription machinery by helping CBP/p300 to recruit new partners into the transcription machinery. Finally, using biotinylated wild-type or acetylated peptides, we find that acetylation decreases Tat's ability to bind the TAR RNA element, as well as to bind basal factors such as TBP, CBP, Core-Pol II, or cyclin T. However, the acetylated Tat peptide is able to bind to core histones on a nucleosome assembled HIV-1 proviral DNA.

Acetylation↗
PubMed2000

Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins.

Susceptibility to multiple sclerosis (MS) is associated with certain MHC class II haplotypes, in particular HLA-DR2. Two DR beta chains, DRB1*1501 and DRB5*0101, are co-expressed in the HLA-DR2 haplotype, resulting in the formation of two functional cell surface heterodimers, HLA-DR2a (DRA*0101, DRB5*0101) and HLA-DR2b (DRA*0101, DRB1*1501). Both isotypes can present an immunodominant peptide of myelin basic protein (MBP 84-102) to MBP-specific T cells from MS patients. We have determined the crystal structure of HLA-DR2a complexed with MBP 86-105 to 1.9 A resolution. A comparison of this structure with that of HLA-DR2b complexed with MBP 85-99, reported previously, reveals that the peptide register is shifted by three residues, such that the MBP peptide is bound in strikingly different conformations by the two MHC molecules. This shift in binding register is attributable to a large P1 pocket in DR2a, which accommodates Phe92, in conjunction with a relatively shallow P4 pocket, which is occupied by Ile95. In DR2b, by contrast, the small P1 pocket accommodates Val89, while the deep P4 pocket is filled by Phe92. In both complexes, however, the C-terminal half of the peptide is positioned higher in the binding groove than in other MHC class II/peptide structures. As a result of the register shift, different side-chains of the MBP peptide are displayed for interaction with T cell receptors in the DR2a and DR2b complexes. These results demonstrate that MHC molecules can impose different alignments and conformations on the same bound peptide as a consequence of topological differences in their peptide-binding sites, thereby creating distinct T cell epitopes.

Alleles↗
PubMed2000

Structural determination of lipid-bound ApoA-I using fluorescence resonance energy transfer.

Based on the x-ray crystal structure of lipid-free Delta43 apoA-I, two monomers of apoA-I were suggested to bind to a phospholipid bilayer in an antiparallel paired dimer, or "belt orientation." This hypothesis challenges the currently held model in which each of the two apoA-I monomers fold as antiparallel alpha-helices or "picket fence orientation." When apoA-I is bound to a phospholipid disc, the first model predicts that the glutamine at position 132 on one apoA-I molecule lies within 16 A of glutamine 132 in the second monomer, whereas, the second model predicts glutamines at position 132 to be 104 A apart. To distinguish between these models, glutamine at position 132 was mutated to cysteine in wild-type apoA-I to produce Q132C apoA-I, which were labeled with thiol-reactive fluorescent probes. Q132C apoA-I was labeled with either fluorescein (donor probe) or tetramethylrhodamine (acceptor probe) and then used to make recombinant phospholipid discs (recombinant high density lipoprotein (rHDL)). The rHDL containing donor- and acceptor-labeled Q132C apoA-I were of similar size, composition, and lecithin:cholesterol acyltransferase reactivity when compared to rHDL-containing human plasma apoA-I. Analysis of donor probe fluorescence showed highly efficient quenching in rHDL containing one donor- and one acceptor-labeled Q132C apoA-I. rHDL containing only acceptor probe-labeled Q132C apoA-I showed rhodamine self-quenching. Both of these observations demonstrate that position 132 in two lipid-bound apoA-I monomers were in close proximity, supporting the "belt conformation" hypothesis for apoA-I on rHDL.

Apolipoprotein A-I↗
PubMed2000

Dissimilar immunogenicities of human papillomavirus E7 and adenovirus E1A proteins influence primary tumor development.

Although human papillomaviruses (HPV) and adenoviruses (Ad) both transform cells by expressing functionally related oncogenes (Ad-E1A/E1B; HPV-E7/E6), only HPV are oncogenic in humans. Prior studies have shown that HPV-transformed cells are resistant to NK cell lysis and E7- and E6-specific CTL are inefficiently generated in women with HPV-induced cervical cancer. Therefore, we postulated that the dissimilar oncogenicities of Ad and HPV may be caused by a protective NK and T cell response that is triggered by transformed cells expressing E1A, but not by E7. To test this hypothesis, mice that were either immunologically intact, lacked T cells, or lacked both NK and T cells were challenged with Ad serotype 5 (Ad5)-E1A- or HPV16-E7-transfected tumor cells. E7-expressing tumor cells were resistant to NK cell lysis in vitro and failed to elicit a measurable anti-tumor NK or T cell response in vivo. The concomitant expression of E6 did not change this phenotype. In contrast, E1A-expressing tumor cells were sensitive to NK lysis in vitro and triggered a protective NK and T cell immune response in vivo. These data suggest differences in the capacities of E1A or E7 oncoproteins to trigger protective anti-tumor immune responses may contribute to the dissimilar oncogenicities of Ad and HPV in humans.

Adenovirus E1A Proteins↗
PubMed2000

Adenosine action on interneurons and synaptic transmission onto interneurons in rat hippocampus in vitro.

To investigate the action of adenosine on interneurons as well as on excitatory synaptic transmission onto interneurons in the hippocampus, intracellular recordings were made from electrophysiologically identified interneurons in the CA1 region of the hippocampal slice in vitro. The effects of adenosine and the preferential adenosine A1 receptor agonist, chloroadenosine, were examined. Application of 50 microM adenosine and 20 microM chloroadenosine to the bath produced a hyperpolarization of 5.6+/-1.6 (n=5) and 6.1+/-1.4 mV (n=6), respectively, as well as a decrease in membrane input resistance of 18.1+/-3.5% (n=5) and 18.5+/-1.4% (n=6), respectively. Adenosine depressed the postsynaptic potentials (PSPs) elicited in the interneurons by stimulation of Schaffer collateral fibers by 73+/-6.8% (n=5). The amplitude and the duration of the afterhyperpolarization which followed the spike of the action potential were attenuated by 48+/-6.9% and 31+/-8.6%, respectively (n=5). Chloroadenosine depressed the evoked PSPs in these interneurons by 61.2+/-2.7% (n=6) and depressed the duration and the amplitude of the afterhyperpolarization by 85.2+/-4.5% and by 72.6+/-4.8%, respectively (n=6). The data show that adenosine and chloroadenosine directly inhibit hippocampal CA1 interneurons by blocking the synaptic input, by hyperpolarizing the membrane potential and by depressing the afterhyperpolarization following individual action potential spikes. It is proposed that adenosine A1 receptors are present at pre- and/or postsynaptic sites of interneuron synapses in the hippocampal CA1 region. The present findings demonstrate that adenosine A1 receptor activation in CA1 interneurons is able to modulate the excitatory synaptic input to, and excitability of, these neurons. Thus, as adenosine is released during ischemia and epilepsy, adenosine may protect both interneurons and pyramidal cells from glutamate excitotoxicity through activation of adenosine A1 receptors on these neurons in the hippocampus.

2-Chloroadenosine↗
PubMed2000

NMR line-broadening and transferred NOESY as a medicinal chemistry tool for studying inhibitors of the hepatitis C virus NS3 protease domain.

This work describes the use of NMR as a medicinal chemistry tool for better understanding the binding characteristics of inhibitors of the HCV NS3 protease. The protease-bound structure of a tetrapeptide-like inhibitor that has an acid C-terminus, a norvaline at P1 and a naphthylmethoxy proline at P2 is described. Conformational comparisons are made with a similar compound having a 1-amino-cyclopropylcarboxylic acid at P1 and with a hexapeptide inhibitor. Differences between the free and bound states are identified. 19F NMR also helped in determining that a single complex is observed when an inhibitor is added to the protease at a 1:1 ratio.

Hepacivirus↗
PubMed2000

Dynamin II regulates hormone secretion in neuroendocrine cells.

The dynamin family of GTP-binding proteins has been implicated as playing an important role in endocytosis. In Drosophila shibire, mutations of the single dynamin gene cause blockade of endocytosis and neurotransmitter release, manifest as temperature-sensitive neuromuscular paralysis. Mammals express three dynamin genes: the neural specific dynamin I, ubiquitous dynamin II, and predominantly testicular dynamin III. Mutations of dynamin I result in a blockade of synaptic vesicle recycling and receptor-mediated endocytosis. Here, we show that dynamin II plays a key role in controlling constitutive and regulated hormone secretion from mouse pituitary corticotrope (AtT20) cells. Dynamin II is preferentially localized to the Golgi apparatus where it interacts with G-protein betagamma subunit and regulates secretory vesicle release. The presence of dynamin II at the Golgi apparatus and its interaction with the betagamma subunit are mediated by the pleckstrin homology domain of the GTPase. Overexpression of the pleckstrin homology domain, or a dynamin II mutant lacking the C-terminal SH3-binding domain, induces translocation of endogenous dynamin II from the Golgi apparatus to the plasma membrane and transformation of dynamin II from activity in the secretory pathway to receptor-mediated endocytosis. Thus, dynamin II regulates secretory vesicle formation from the Golgi apparatus and hormone release from mammalian neuroendocrine cells.

Amino Acid Sequence↗
PubMed2000

Synthesis of galactosyl and lactosyl derivatives as potential anti-metastasis compounds.

Based on the known anti-metastasis activities of lactosides and galactosides, a galactosyl and a lactosyl trimannoside were prepared via the conventional Koenigs-Knorr and trichloroacetimidate methods, respectively. Through typical deblocking procedures, a tetrasaccharide alpha-D-Galp-(1 --> 2)-alpha-D-Manp-(1 --> 2)-alpha-D-Manp-(1 --> 6)-alpha-D-ManpOCH3 and a pentasaccharide beta-D-Galp-(1 --> 4)-beta-D-Glcp-(1 --> 2)-alpha-D-Manp-(1 --> 2)-alpha-D-Manp-(1 --> 6)-alpha-D-ManpOCH3 were obtained.

Antineoplastic Agents↗
PubMed2000

Crystal structure of a thermophilic cytochrome P450 from the archaeon Sulfolobus solfataricus.

The structure of the first P450 identified in Archaea, CYP119 from Sulfolobus solfataricus, has been solved in two different crystal forms that differ by the ligand (imidazole or 4-phenylimidazole) coordinated to the heme iron. A comparison of the two structures reveals an unprecedented rearrangement of the active site to adapt to the different size and shape of ligands bound to the heme iron. These changes involve unraveling of the F helix C-terminal segment to extend a loop structure connecting the F and G helices, allowing the longer loop to dip down into the active site and interact with the smaller imidazole ligand. A comparison of CYP119 with P450cam and P450eryF indicates an extensive clustering of aromatic residues may provide the structural basis for the enhanced thermal stability of CYP119. An additional feature of the 4-phenylimidazole-bound structure is a zinc ion tetrahedrally bound by symmetry-related His and Glu residues.

Archaeal Proteins↗