Structure and conformation of the hydrochloride of pseudoisocytidine, an antileukemic C-nucleoside

1980 ◽  
Vol 58 (16) ◽  
pp. 1633-1638 ◽  
Author(s):  
George I. Birnabaum ◽  
Kyoichi A. Watanabe ◽  
Jack J. Fox
Keyword(s):  
Heavy Atom ◽  
Three Dimensional ◽  
Direct Methods ◽  
Dimensional Structure ◽  
Side Chain ◽  
Hydrogen Atoms ◽  
Triclinic Space Group ◽  
X Ray Crystallography ◽  
Cell Dimensions ◽  
Sugar Ring

The three-dimensional structure of pseudoisocytidine hydrochloride was determined by X-ray crystallography. The crystals belong to the triclinic space group P1 and the cell dimensions are a = 6.623(2), b = 8.053(2), c = 6.201(2) Å, α = 108.35(2), β = 101.36(2), γ = 93.54(2) °. Intensity data were measured with a diffractometer and the structure was solved by a combination of heavy-atom and direct methods. Least-squares refinement, which included hydrogen atoms, converged at R = 0.040. The conformation about the glycosyl bond is anti (χCC = 21.6°), the pucker of the furanose ring is C(1′)exo, and the conformation of the —CH2OH side chain is gauche–trans (t). An examination of bond lengths indicates that of the three main resonance forms of the isocytosine cation the fully conjugated one contributes more to the structure than the cross-conjugated one. Bond angles in the sugar ring reflect its rare conformation.

Structure and conformation of the anticodon nucleoside 5-methoxyuridine in the solid state and in solution

1983 ◽  
Vol 61 (10) ◽  
pp. 2299-2304 ◽  
Author(s):  
George I. Birnbaum ◽  
Wayne J. P. Blonski ◽  
Frank E. Hruska
Keyword(s):  
Solid State ◽  
Three Dimensional ◽  
Direct Methods ◽  
Pyrimidine Ring ◽  
Dimensional Structure ◽  
Side Chain ◽  
Monoclinic Space Group ◽  
Hydrogen Atoms ◽  
Cell Dimensions ◽  
Enol Tautomer

The three-dimensional structure of 5-methoxyuridine (mo5U) was determined with much higher precision than in a previous study (Hillen etal. J. Carbohydr. Nucleosides Nucleotides, 5, 23 (1978)). The crystals belong to the monoclinic space group P21 and the cell dimensions are a = 8.916(2), b = 14.372(2), c = 4.714(1) Å, β = 97.44(2)°. Intensity data were measured with a diffractometer and the structure was solved by direct methods. Least-squares refinement, which included all hydrogen atoms, converged at R = 0.031. The conformation about the glycosyl bond is anti (χCN = 23.1°), the pucker of the ribose ring is C(3′)endo, and the conformation of the —CH2OH side chain is gauche+. A comparison of the bond lengths N(3)—C(4) and C(4)—O(4) with those in uridine does not support the conclusion of Hillen etal. about a shift to the enol tautomer in mo5U. However, there are other changes in the geometry of the pyrimidine ring due to substitution at C(5). A conformational analysis, based on 1H and 13C nmr data, shows that the preferred conformation in solution is that observed in the solid state.

Thyroid Hormone Stereochemistry. II. Molecular Structure of Thyronine HCl Ethyl Ester Monohydrate

1974 ◽  
Vol 52 (17) ◽  
pp. 3042-3047 ◽  
Author(s):  
Arthur Camerman ◽  
Norman Camerman
Keyword(s):  
Ethyl Ester ◽  
Three Dimensional ◽  
Chloride Ion ◽  
Dimensional Structure ◽  
Side Chain ◽  
Monoclinic Space Group ◽  
X Ray Diffraction ◽  
Ether Linkage ◽  
Cell Dimensions ◽  
Phenyl Rings

The three-dimensional structure of L-thyronine, the non-iodinated physiologically inactive analog of thyroxine, has been determined by single crystal X-ray diffraction and compared to the active thyroid hormones. The compound crystallized as the monohydrate of thyronine hydrochloride ethyl ester in the monoclinic space group P21 with cell dimensions a = 10.502, b = 5.165, c = 17.940 Å, β = 109.74°. The structure was solved by Patterson methods to find the chloride ion and iterative Fourier maps to locate the rest of the atoms. Refinement was by anisotropic full-matrix least squares to convergence at R = 0.048.The two phenyl rings adopt a twisted orientation with respect to each other with angles of −37° and −67° between the plane of the inter-ring ether linkage and the planes of the α- and β-rings, respectively. This orientation differs considerably from that found in the iodinated thyronines. The conformation of the alanine side chain is remarkably similar to that of the alanine in the iodinated thyronines.

Conformational features of acyclonucleosides: structure of acyclovir, an antiherpes agent

1984 ◽  
Vol 62 (12) ◽  
pp. 2646-2652 ◽  
Author(s):  
George I. Birnbaum ◽  
Miroslaw Cygler ◽  
David Shugar
Keyword(s):  
Direct Methods ◽  
Side Chain ◽  
Asymmetric Unit ◽  
Hydrogen Atoms ◽  
Torsion Angles ◽  
The Third ◽  
Cell Dimensions ◽  
Enzymatic Systems ◽  
Antiviral Activities ◽  
Independent Molecules

Crystals of acyclovir belong to the space group P21/n, and the cell dimensions are a = 25.459(1), b = 11.282 (1), c = 10.768(1) Å, β = 95.16(1)°. Intensity data were measured on a diffractometer and the structure was determined by direct methods. The asymmetric unit was found to contain three independent molecules of acyclovir and two molecules of water. Least-squares refinement, which included all hydrogen atoms, converged at R = 0.053 for 3970 observed reflections. In two of the molecules the side chain is partially folded, while in the third one it is fully extended. The glycosidic torsion angles are in the range 91.4–104.3°. The conformational features are compared with those in other known acyclonucleosides. They are also examined in relation to the behavior of acyclonucleosides and acyclonucleotides in various enzymatic systems, including those related to antiviral activities.

Structure and conformation of 3′-azido-3′-deoxythymidine (AZT), an inhibitor of the HIV (AIDS) virus

1987 ◽  
Vol 65 (9) ◽  
pp. 2135-2139 ◽  
Author(s):  
George I. Birnbaum ◽  
Jerzy Giziewicz ◽  
Eric J. Gabe ◽  
Tai-Shun Lin ◽  
William H. Prusoff
Keyword(s):  
Active Form ◽  
Three Dimensional ◽  
Direct Methods ◽  
High Energy ◽  
Biologically Active ◽  
Dimensional Structure ◽  
Human Immunodeficiency Virus Replication ◽  
Monoclinic Space Group ◽  
Sugar Ring ◽  
Immunodeficiency Syndrome

3′-Azido-3′-deoxythymidine (AZT), an inhibitor of HIV (human immunodeficiency virus) replication, was recently found to improve the condition of patients suffering from AIDS (acquired immunodeficiency syndrome) or ARC (AIDS-related complex). An X-ray analysis of AZT was undertaken in order to determine the three-dimensional structure of this thymidine analogue. The crystals belong to the monoclinic space group P21 and the cell dimensions are a = 5.6282(4), b = 12.0130(7), c = 17.5072(10) Å, β = 95.946(5)°. The structure was determined by direct methods and refined to R = 0.028 for 2029 observed reflections. Two crystallographically independent molecules were found in the asymmetric unit. One of them, molecule A, adopts a conformation which is fairly common in nucleosides, viz. a C2′ endo/C3′ exo pucker of the furanose ring and a glycosidic torsion angle χCN = 53.4°. However, the conformation of molecule B is highly unusual. The sugar ring pucker is C3′ exo/C4′ endo and χCN = 2.3°. This high-energy conformation may represent the biologically active form of AZT. Its determination may therefore assist in the design of other inhibitors of HIV.

Structure and conformation of 5-methoxymethyl-2′-deoxycytidine

1990 ◽  
Vol 68 (6) ◽  
pp. 836-841 ◽  
Author(s):  
Zongchao Jia ◽  
Guy Tourigny ◽  
Louis T. J. Delbaere ◽  
Allan L. Stuart ◽  
Sagar V. Gupta
Keyword(s):  
Three Dimensional ◽  
Antiviral Agent ◽  
Crystallographic Analysis ◽  
Dimensional Structure ◽  
Side Chain ◽  
X Ray ◽  
Envelope Conformation ◽  
Anti Conformation ◽  
Sugar Ring ◽  
Antiherpes Activity

The three-dimensional structure of the antiviral agent 5-methoxymethyl-2′-deoxycytidine (MMdCyd) was deduced by X-ray crystallographic analysis. MMdCyd crystallized in space group P21 with a = 7.9255(6) Å; b = 16.1505(15) Å, c = 10.1861(5) Å, β = 103.801(5)°, and Z = 4 (2 molecules per asymmetric unit); R = 0.044 (Rw = 0.046) for 2560 observed reflections with net I > 3σ(I). The furanose ring adopts the C(3′)-exo envelope conformation (3E) in molecule A and the C(2′)-endo envelope conformation (2E) in molecule B. In the sugar ring of both crystallographically independent molecules A and B, the side chain at C(5′) has the g+ conformation. This appears to be a preferred geometry required for antiherpes activity in 2′-deoxyribonucleosides. The glycosyl linkage is anti with χ = 213.7° for the A molecule and 222.2° for the B molecule. With respect to this anti conformation, the methoxy group at C(5) in molecules A and B exhibits different conformations; it is on the same side of the pyrimidine plane as the deoxyribofuranose ring oxygen (O4′) in molecule B and on the opposite side in molecule A. Keywords: antiherpes agent, conformation, 5-methoxymethyl-2′-deoxycytidine, crystal structure.

X-ray and 1H nmr analyses of 5-(m-benzyloxybenzyl)-1-[(1,3-dihydroxy-2-propoxy)methyl]uracil, an acyclonucleoside inhibitor of uridine phosphorylase

1986 ◽  
Vol 64 (12) ◽  
pp. 2376-2381 ◽  
Author(s):  
George I. Birnbaum ◽  
Jean-Robert Brisson ◽  
Shi Hsi Chu ◽  
Zhi Hao Chen ◽  
Elizabeth C. Rowe
Keyword(s):  
Direct Methods ◽  
Uridine Phosphorylase ◽  
Hydrogen Atoms ◽  
Gauche Conformation ◽  
Triclinic Space Group ◽  
X Ray ◽  
H Nmr ◽  
Cell Dimensions ◽  
Nuclear Overhauser ◽  
Glycosidic Torsion Angle

The title compound crystallizes in the triclinic space group [Formula: see text] and the cell dimensions are a = 16.890(3), b = 9.586(2), c = 6.316(1) Å, α = 91.09(1), β = 93.50(1), γ = 93.04(1)°. X-ray intensity data were measured on a diffractometer, and the crystal structure was determined by direct methods. Least-squares refinement, which included all hydrogen atoms, converged at R = 0.056 for 3454 observed reflections. Adjacent six-membered rings are approximately perpendicular to one another. The glycosidic torsion angle [C(6)—N(1)—C(1′)—O(4′)] is 96.2(2)°. In the acyclic moiety, both C—OH bonds are gauche with respect to C(4′)—O(4′). The gauche conformation is also dominant in solution, as determined by high-resolution 1H nmr spectroscopy. Results of nuclear Overhauser experiments lead to conclusions about the flexibility of the molecule.

Structure and conformation of 5′-chloro-5′-deoxyarabinosylcytosine: X-ray, 1H and 13C nmr analyses

1988 ◽  
Vol 66 (5) ◽  
pp. 1203-1208 ◽  
Author(s):  
George I. Birnbaum ◽  
Miloš Buděšínský ◽  
Jiří Beránek
Keyword(s):  
Direct Methods ◽  
Acid Synthesis ◽  
Side Chain ◽  
Hydrogen Atoms ◽  
Orthorhombic Space Group ◽  
1H And 13C Nmr ◽  
X Ray ◽  
Anti Conformation ◽  
Cell Dimensions ◽  
Equal Population

Crystals of 5′-chloroarabinosylcytosine, an inhibitor of nucleic acid synthesis, belong to the orthorhombic space group P212121, and the cell dimensions are a = 6.801(1), b = 9.698(2) and c = 16.497(3) Å. X-ray intensity data were measured on a diffractometer and the structure was determined by direct methods. Least-squares refinement, which included all hydrogen atoms, converged at R = 0.032 for 1251 observed reflections. The conformation about the glycosyl bond is anti, the furanose ring adopts a C3′ endo/C4′ exo pucker and the conformation of the side chain is gauche+, stabilized by an intramolecular [Formula: see text] hydrogen bond. 1H and 13C nmr spectra confirm the anti conformation about the glycosyl bond. In D2O solution there is an approximately equal population of N- and S-type conformers of the furanose ring and a trans > gauche+ > gauche− distribution of the 5′-CH2Cl side chain rotamers.

Configurational and conformational studies on condensation products of biogenic amines with 2,5-anhydro-D-mannose

1985 ◽  
Vol 63 (11) ◽  
pp. 2915-2921 ◽  
Author(s):  
Ian M. Piper ◽  
David B. MacLean ◽  
Romolo Faggiani ◽  
Colin J. L. Lock ◽  
Walter A. Szarek
Keyword(s):  
Hydrogen Bond ◽  
Intermolecular Hydrogen Bond ◽  
Direct Methods ◽  
Conformational Studies ◽  
X Ray ◽  
X Ray Crystallography ◽  
H Nmr ◽  
Twist Conformation ◽  
Cell Dimensions ◽  
Internal Hydrogen Bond

The products of a Pictet–Spengler condensation of tryptamine and of histamine with 2,5-anhydro-D-mannose have been studied by X-ray crystallography to establish their absolute configuration. 1(S)-(α-D-Arabinofuranosyl)-1,2,3,4-tetrahydro-β-carboline (1), C16H20N20O4, is monoclinic, P21 (No. 4), with cell dimensions a = 13.091(4), b = 5.365(1), c = 11.323(3) Å, β = 115.78(2)°, and Z = 2. 4-(α-D-Arabinofuranosyl)imidazo[4,5-c]-4,5,6,7-tetrahydropyridine (3), C11H17N3O4, is orthorhombic, P212121 (No. 19), with cell dimensions a = 8.118(2), b = 13.715(4), c = 10.963(3) Å, and Z = 4. The structures were determined by direct methods and refined to R1 = 0.0514, R2 = 0.0642 for 3210 reflections in the case of 1, and to R1 = 0.0312, R2 = 0.0335 for 1569 reflections in the case of 3. Bond lengths and angles within both molecules are normal and agree well with those observed in related structures. In 3 the base and sugar adopt a syn arrangement, which is maintained by an internal hydrogen bond between O(2′) and N(3). The sugar adopts a normal 2T3 twist conformation. The sugar has the opposite anti arrangement in the β-carboline 1 and the conformation of the sugar is unusual; it is close to an envelope conformation with O(4′) being the atom out of the plane. This conformation is caused by a strong intermolecular hydrogen bond from O(5′) in a symmetry-related molecule to O(4′). Both compounds are held together in the crystal by extensive hydrogen-bonding networks. The conformations of the compounds in solution have been investigated by 1H nmr spectroscopy, and the results obtained were compared with those obtained by X-ray crystallography for 1 and 3.

Crystal structure of the hinge domain of Smchd1 reveals its dimerization mode and nucleic acid–binding residues

2020 ◽  
Vol 13 (636) ◽  
pp. eaaz5599 ◽  
Author(s):  
Kelan Chen ◽  
Richard W. Birkinshaw ◽  
Alexandra D. Gurzau ◽  
Iromi Wanigasuriya ◽  
Ruoyun Wang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Muscular Dystrophy ◽  
Three Dimensional ◽  
Underlying Mechanism ◽  
Structural Features ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Dimensional Structure ◽  
Nucleic Acid Binding ◽  
X Ray Crystallography ◽  
Hinge Domain

Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) is an epigenetic regulator in which polymorphisms cause the human developmental disorder, Bosma arhinia micropthalmia syndrome, and the degenerative disease, facioscapulohumeral muscular dystrophy. SMCHD1 is considered a noncanonical SMC family member because its hinge domain is C-terminal, because it homodimerizes rather than heterodimerizes, and because SMCHD1 contains a GHKL-type, rather than an ABC-type ATPase domain at its N terminus. The hinge domain has been previously implicated in chromatin association; however, the underlying mechanism involved and the basis for SMCHD1 homodimerization are unclear. Here, we used x-ray crystallography to solve the three-dimensional structure of the Smchd1 hinge domain. Together with structure-guided mutagenesis, we defined structural features of the hinge domain that participated in homodimerization and nucleic acid binding, and we identified a functional hotspot required for chromatin localization in cells. This structure provides a template for interpreting the mechanism by which patient polymorphisms within the SMCHD1 hinge domain could compromise function and lead to facioscapulohumeral muscular dystrophy.

MRPC (Missing Regions in Polypeptide Chains): a knowledgebase

2019 ◽  
Vol 52 (6) ◽  
pp. 1422-1426
Author(s):  
Rajendran Santhosh ◽  
Namrata Bankoti ◽  
Adgonda Malgonnavar Padmashri ◽  
Daliah Michael ◽  
Jeyaraman Jeyakanthan ◽  
...  
Keyword(s):  
Protein Structures ◽  
Three Dimensional ◽  
Protein Molecule ◽  
Data Bank ◽  
Protein Crystal ◽  
Dimensional Structure ◽  
Protein Structure Analysis ◽  
Three Dimensional Structure ◽  
X Ray Crystallography ◽  
Polypeptide Chains

Missing regions in protein crystal structures are those regions that cannot be resolved, mainly owing to poor electron density (if the three-dimensional structure was solved using X-ray crystallography). These missing regions are known to have high B factors and could represent loops with a possibility of being part of an active site of the protein molecule. Thus, they are likely to provide valuable information and play a crucial role in the design of inhibitors and drugs and in protein structure analysis. In view of this, an online database, Missing Regions in Polypeptide Chains (MRPC), has been developed which provides information about the missing regions in protein structures available in the Protein Data Bank. In addition, the new database has an option for users to obtain the above data for non-homologous protein structures (25 and 90%). A user-friendly graphical interface with various options has been incorporated, with a provision to view the three-dimensional structure of the protein along with the missing regions using JSmol. The MRPC database is updated regularly (currently once every three months) and can be accessed freely at the URL http://cluster.physics.iisc.ac.in/mrpc.

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