Crystal Structures of MMP-9 Complexes with Five Inhibitors: Contribution of the Flexible Arg424 Side-chain to Selectivity

2007 ◽  
Vol 371 (4) ◽  
pp. 989-1006 ◽  
Author(s):  
Anna Tochowicz ◽  
Klaus Maskos ◽  
Robert Huber ◽  
Ruth Oltenfreiter ◽  
Vincent Dive ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Side Chain

Structural Studies on N-(2,4,6-Trimethylphenyl)-methyl/ chloro-acetamides, 2,4,6-(CH3)3C6H2NH-CO-CH3–yXy (X = CH3 or Cl and y = 0, 1, 2)

2006 ◽  
Vol 61 (10-11) ◽  
pp. 588-594 ◽  
Author(s):  
Basavalinganadoddy Thimme Gowda ◽  
Jozef Kožíšek ◽  
Hartmut Fuess
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Structural Data ◽  
The Other ◽  
Side Chain ◽  
Structural Studies ◽  
Asymmetric Unit ◽  
Lattice Constants ◽  
Peptide Linkage ◽  
The Mean

TMPAThe effect of substitutions in the ring and in the side chain on the crystal structure of N- (2,4,6-trimethylphenyl)-methyl/chloro-acetamides of the configuration 2,4,6-(CH3)3C6H2NH-COCH3− yXy (X = CH3 or Cl and y = 0,1, 2) has been studied by determining the crystal structures of N-(2,4,6-trimethylphenyl)-acetamide, 2,4,6-(CH3)3C6H2NH-CO-CH3 (); N-(2,4,6- trimethylphenyl)-2-methylacetamide, 2,4,6-(CH3)3C6H2NH-CO-CH2-CH3 (TMPMA); N-(2,4,6- trimethylphenyl)-2,2-dimethylacetamide, 2,4,6-(CH3)3C6H2NH-CO-CH(CH3)2 (TMPDMA) and N-(2,4,6-trimethylphenyl)-2,2-dichloroacetamide, 2,4,6-(CH3)3C6H2NH-CO-CHCl2 (TMPDCA). The crystallographic system, space group, formula units and lattice constants in Å are: TMPA: monoclinic, Pn, Z = 2, a = 8.142(3), b = 8.469(3), c = 8.223(3), β = 113.61(2)◦; TMPMA: monoclinic, P21/n, Z = 8, a = 9.103(1), b = 15.812(2), c = 16.4787(19), α = 89.974(10)◦, β = 96.951(10)◦, γ =89.967(10)◦; TMPDMA: monoclinic, P21/c, Z = 4, a =4.757(1), b= 24.644(4), c =10.785(2), β = 99.647(17)◦; TMPDCA: triclinic, P¯1, Z = 2, a = 4.652(1), b = 11.006(1), c = 12.369(1), α = 82.521(7)◦, β = 83.09(1)◦, γ = 79.84(1)◦. The results are analyzed along with the structural data of N-phenylacetamide, C6H5NH-CO-CH3; N-(2,4,6-trimethylphenyl)-2-chloroacetamide, 2,4,6-(CH3)3C6H2NH-CO-CH2Cl; N-(2,4,6-trichlorophenyl)-acetamide, 2,4,6-Cl3C6H2NH-COCH3; N-(2,4,6-trichlorophenyl)-2-chloroacetamide, 2,4,6-Cl3C6H2NH-CO-CH2Cl; N-(2,4,6-trichlorophenyl)- 2,2-dichloroacetamide, 2,4,6-Cl3C6H2NH-CO-CHCl2 and N-(2,4,6-trichlorophenyl)- 2,2,2-trichloroacetamide, 2,4,6-Cl3C6H2NH-CO-CCl3. TMPA, TMPMA and TMPDCA have one molecule each in their asymmetric units, while TMPDMA has two molecules in its asymmetric unit. Changes in the mean ring distances are smaller on substitution as the effect has to be transmitted through the peptide linkage. The comparison of the other bond parameters reveal that there are significant changes in them on substitution.

scholarly journals Conformation-dependent restraints for polynucleotides: the sugar moiety

2019 ◽  
Vol 48 (2) ◽  
pp. 962-973
Author(s):  
Marcin Kowiel ◽  
Dariusz Brzezinski ◽  
Miroslaw Gilski ◽  
Mariusz Jaskolski
Keyword(s):  
Nucleic Acids ◽  
Crystal Structures ◽  
Protein Data Bank ◽  
Data Bank ◽  
Experimental Methods ◽  
Side Chain ◽  
Torsion Angles ◽  
Sugar Moiety ◽  
Structural Database ◽  
Different Parts

Abstract Stereochemical restraints are commonly used to aid the refinement of macromolecular structures obtained by experimental methods at lower resolution. The standard restraint library for nucleic acids has not been updated for over two decades and needs revision. In this paper, geometrical restraints for nucleic acids sugars are derived using information from high-resolution crystal structures in the Cambridge Structural Database. In contrast to the existing restraints, this work shows that different parts of the sugar moiety form groups of covalent geometry dependent on various chemical and conformational factors, such as the type of ribose or the attached nucleobase, and ring puckering or rotamers of the glycosidic (χ) or side-chain (γ) torsion angles. Moreover, the geometry of the glycosidic link and the endocyclic ribose bond angles are functionally dependent on χ and sugar pucker amplitude (τm), respectively. The proposed restraints have been positively validated against data from the Nucleic Acid Database, compared with an ultrahigh-resolution Z-DNA structure in the Protein Data Bank, and tested by re-refining hundreds of crystal structures in the Protein Data Bank. The conformation-dependent sugar restraints presented in this work are publicly available in REFMAC, PHENIX and SHELXL format through a dedicated RestraintLib web server with an API function.

scholarly journals Structures of the antibody 64M-5 Fab and its complex with dT(6–4)T indicate induced-fit and high-affinity mechanisms

2019 ◽  
Vol 75 (2) ◽  
pp. 80-88 ◽  
Author(s):  
Hideshi Yokoyama ◽  
Ryuta Mizutani ◽  
Shuji Noguchi ◽  
Naoki Hayashida
Keyword(s):  
Crystal Structures ◽  
Ultraviolet Light ◽  
Electrostatic Interaction ◽  
Side Chain ◽  
Induced Fit ◽  
Phosphate Moiety ◽  
High Affinity ◽  
Dna Photoproducts ◽  
Complementarity Determining Region

DNA photoproducts with (6–4) pyrimidine–pyrimidone adducts produced by ultraviolet light are mutagenic and carcinogenic. The crystal structures of the anti-(6–4) photoproduct antibody 64M-5 Fab and of its complex with dT(6–4)T were determined at 2.5 and 2.0 Å resolution, respectively. A comparison between the dT(6–4)T-liganded and unliganded structures indicates that the side chain of His93L is greatly rotated and shifted on binding to dT(6–4)T, leading to the formation of an electrostatic interaction with the phosphate moiety of dT(6–4)T, which shows a remarkable induced fit. Based on a comparison of the dT(6–4)T-liganded structures of the 64M-5 and 64M-2 Fabs, the electrostatic interaction between the side chain of His93L in 64M-5 and the phosphate moiety of dT(6–4)T is lost for Leu93L in 64M-2, while Arg90L in 64M-5 instead of Gln90L in 64M-2 stabilizes the conformation of complementarity-determining region (CDR) L3. These differences contribute to the higher affinity of 64M-5 for dT(6–4)T compared with that of 64M-2.

The Conformation of the Side Chain of 21-Alkylpregnanes

2003 ◽  
Vol 2003 (9) ◽  
pp. 556-558 ◽  
Author(s):  
James R. Hanson ◽  
Peter B. Hitchcock ◽  
Jorge A.R. Salvador
Keyword(s):  
Crystal Structures ◽  
Side Chain ◽  
Methyl Group ◽  
X Ray

The X-ray crystal structures of some 21-alkylpregnanes have been determined and the effects of a 16α,17α-epoxide and 21-methyl group on the conformation of the side chain are discussed.

scholarly journals Crystal Structures of Cytochrome P450 105P1 from Streptomyces avermitilis: Conformational Flexibility and Histidine Ligation State

2008 ◽  
Vol 191 (4) ◽  
pp. 1211-1219 ◽  
Author(s):  
Lian-Hua Xu ◽  
Shinya Fushinobu ◽  
Haruo Ikeda ◽  
Takayoshi Wakagi ◽  
Hirofumi Shoun
Keyword(s):  
Crystal Structures ◽  
Biosynthetic Pathway ◽  
Heme Iron ◽  
Streptomyces Avermitilis ◽  
Side Chain ◽  
Wild Type ◽  
Loop Region ◽  
Polyene Macrolide Antibiotic ◽  
Spectroscopic Characteristics ◽  
Ligand Free

ABSTRACT The polyene macrolide antibiotic filipin is widely used as a probe for cholesterol in biological membranes. The filipin biosynthetic pathway of Streptomyces avermitilis contains two position-specific hydroxylases, C26-specific CYP105P1 and C1′-specific CYP105D6. In this study, we describe the three X-ray crystal structures of CYP105P1: the ligand-free wild-type (WT-free), 4-phenylimidazole-bound wild-type (WT-4PI), and ligand-free H72A mutant (H72A-free) forms. The BC loop region in the WT-free structure has a unique feature; the side chain of His72 within this region is ligated to the heme iron. On the other hand, this region is highly disordered and widely open in WT-4PI and H72A-free structures, respectively. Histidine ligation of wild-type CYP105P1 was not detectable in solution, and a type II spectral change was clearly observed when 4-phenylimidazole was titrated. The H72A mutant showed spectroscopic characteristics that were almost identical to those of the wild-type protein. In the H72A-free structure, there is a large pocket that is of the same size as the filipin molecule. The highly flexible feature of the BC loop region of CYP105P1 may be required to accept a large hydrophobic substrate.

Nitration of 2,3,4,6-Tetramethylphenol and 1,2,3,5-Tetramethylbenzene

1985 ◽  
Vol 38 (4) ◽  
pp. 587 ◽  
Author(s):  
MP Hartshorn ◽  
JM Readman ◽  
WT Robinson ◽  
J Vaughan
Keyword(s):  
Nitric Acid ◽  
Nitrogen Dioxide ◽  
Crystal Structures ◽  
Side Chain ◽  
X Ray ◽  
Fuming Nitric Acid

Nitration of 1,2,3,5-tetramethylbenzene (2a) with fuming nitric acid gives the tetramethylnitrobenzene (22), products of side-chain modification (23)-(27), the rearranged 6,6-dimethylcyclohexenones (8), (28), (29) and (30), and 2,3,4,6-tetramethyl ketone derivatives (10)- (13), (31) and (32). Reaction of 2,3,4,6-tetramethylphenol (7) with nitrogen dioxide gives the hydroxy dinitro ketone (9) in addition to the trinitrocyclohexenones (11)-(14) and (19). X-ray crystal structures are reported for compounds (11), (19), (28), (29), (30) and (32). 1H n.m.r ./stereochemistry correlations are reported for some 2,5-dinitro- and 2,5,6-trinitro-cyclohex-3-enones.

scholarly journals Crystal structures of two monomeric triosephosphate isomerase variants identifiedviaa directed-evolution protocol selecting forL-arabinose isomerase activity

2016 ◽  
Vol 72 (6) ◽  
pp. 490-499
Author(s):  
Mirja Krause ◽  
Tiila-Riikka Kiema ◽  
Peter Neubauer ◽  
Rik K. Wierenga
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Directed Evolution ◽  
Crystal Structures ◽  
Active Site ◽  
Triosephosphate Isomerase ◽  
Point Mutations ◽  
Van Der Waals Interactions ◽  
Side Chain ◽  
Arabinose Isomerase

The crystal structures are described of two variants of A-TIM: Ma18 (2.7 Å resolution) and Ma21 (1.55 Å resolution). A-TIM is a monomeric loop-deletion variant of triosephosphate isomerase (TIM) which has lost the TIM catalytic properties. Ma18 and Ma21 were identified after extensive directed-evolution selection experiments using anEscherichia coliL-arabinose isomerase knockout strain expressing a randomly mutated A-TIM gene. These variants facilitate better growth of theEscherichia coliselection strain in medium supplemented with 40 mML-arabinose. Ma18 and Ma21 differ from A-TIM by four and one point mutations, respectively. Ma18 and Ma21 are more stable proteins than A-TIM, as judged from CD melting experiments. Like A-TIM, both proteins are monomeric in solution. In the Ma18 crystal structure loop 6 is open and in the Ma21 crystal structure loop 6 is closed, being stabilized by a bound glycolate molecule. The crystal structures show only small differences in the active site compared with A-TIM. In the case of Ma21 it is observed that the point mutation (Q65L) contributes to small structural rearrangements near Asn11 of loop 1, which correlate with different ligand-binding properties such as a loss of citrate binding in the active site. The Ma21 structure also shows that its Leu65 side chain is involved in van der Waals interactions with neighbouring hydrophobic side-chain moieties, correlating with its increased stability. The experimental data suggest that the increased stability and solubility properties of Ma21 and Ma18 compared with A-TIM cause better growth of the selection strain when coexpressing Ma21 and Ma18 instead of A-TIM.

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