High-resolution crystal structure of spin labelled (T21R1) azurin from Pseudomonas aeruginosa: a challenging structural benchmark for in silico spin labelling algorithms

ABSTRACTMetallo-β-lactamase (MBL) genes confer resistance to virtually all β-lactam antibiotics and are rapidly disseminated by mobile genetic elements in Gram-negative bacteria. MBLs belong to three different subgroups, B1, B2, and B3, with the mobile MBLs largely confined to subgroup B1. The B3 MBLs are a divergent subgroup of predominantly chromosomally encoded enzymes. AIM-1 (AdelaideIMipenmase 1) fromPseudomonas aeruginosawas the first B3 MBL to be identified on a readily mobile genetic element. Here we present the crystal structure of AIM-1 and usein silicodocking and quantum mechanics and molecular mechanics (QM/MM) calculations, together with site-directed mutagenesis, to investigate its interaction with β-lactams. AIM-1 adopts the characteristic αβ/βα sandwich fold of MBLs but differs from other B3 enzymes in the conformation of an active site loop (residues 156 to 162) which is involved both in disulfide bond formation and, we suggest, interaction with substrates. The structure, together with docking and QM/MM calculations, indicates that the AIM-1 substrate binding site is narrower and more restricted than those of other B3 MBLs, possibly explaining its higher catalytic efficiency. The location of Gln157 adjacent to the AIM-1 zinc center suggests a role in drug binding that is supported by ourin silicostudies. However, replacement of this residue by either Asn or Ala resulted in only modest reductions in AIM-1 activity against the majority of β-lactam substrates, indicating that this function is nonessential. Our study reveals AIM-1 to be a subclass B3 MBL with novel structural and mechanistic features.

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The crystal structure of PD1, aHaemophilussurface fibril domain

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x17001406 ◽

2017 ◽

Vol 73 (2) ◽

pp. 101-108 ◽

Cited By ~ 2

Author(s):

Jack Wright ◽

Maren Thomsen ◽

Robert Kolodziejczyk ◽

Joshua Ridley ◽

Jessica Sinclair ◽

...

Keyword(s):

Crystal Structure ◽

High Resolution ◽

Electron Micrographs ◽

In Silico ◽

Structural Data ◽

Domain Annotation ◽

Virulent Strains ◽

Trimeric Autotransporter Adhesin ◽

Putative Domain

TheHaemophilussurface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains ofH. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel `hairpin-like' architecture, the characterization of Hsf has been limited toin silicomodelling and electron micrographs, with no high-resolution structural data available. Here, the crystal structure of Hsf putative domain 1 (PD1) is reported at 3.3 Å resolution. The structure corrects the previous domain annotation by revealing the presence of an unexpected N-terminal TrpRing domain. PD1 represents the first Hsf domain to be solved, and thus paves the way for further research on the `hairpin-like' hypothesis.

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High resolution STEM imaging study on high Tc superconductor YBa2CuaO7-x

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100106478 ◽

1988 ◽

Vol 46 ◽

pp. 882-883

Author(s):

H.-J. Ou ◽

J. M. Cowley

Keyword(s):

Crystal Structure ◽

High Resolution ◽

Grain Boundary ◽

Strong Field ◽

Imaging Study ◽

Structure Defects ◽

High Tc ◽

High Tc Superconductor ◽

Diffraction Patterns ◽

Lattice Planes

Using the dedicate VG-HB5 STEM microscope, the crystal structure of high Tc superconductor of YBa2Cu3O7-x has been studied via high resolution STEM (HRSTEM) imaging and nanobeam (∽3A) diffraction patterns. Figure 1(a) and 2(a) illustrate the HRSTEM image taken at 10' times magnification along [001] direction and [100] direction, respectively. In figure 1(a), a grain boundary with strong field contrast is seen between two crystal regions A and B. The grain boundary appears to be parallel to a (110) plane, although it is not possible to determine [100] and [001] axes as it is in other regions which contain twin planes [3]. Following the horizontal lattice lines, from left to right across the grain boundary, a lattice bending of ∽4° is noticed. Three extra lattice planes, indicated by arrows, were found to terminate at the grain boundary and form dislocations. It is believed that due to different chemical composition, such structure defects occur during crystal growth. No bending is observed along the vertical lattice lines.

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Perovskite Solar Cells: Crystal Structure and Interface Architecture with High Resolution TEM Observations

10.29363/nanoge.ap-hopv.2018.028 ◽

2017 ◽

Author(s):

Satoshi Uchida ◽

Tae Woong Kim ◽

Ludmila Cojocaru ◽

Takashi Kondo ◽

Hiroshi Segawa

Keyword(s):

Crystal Structure ◽

Solar Cells ◽

High Resolution ◽

Perovskite Solar Cells ◽

High Resolution Tem

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Faculty Opinions recommendation of High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1092564.553651 ◽

2008 ◽

Author(s):

Marc Caron

Keyword(s):

Crystal Structure ◽

High Resolution ◽

G Protein ◽

G Protein Coupled Receptor ◽

G Protein Coupled

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Design, Synthesis and In-Vitro Biological Activity of Some New 1,3-Thiazolidine-4-One Derivatives as Chemotherapeutic Agents Using Virtual Screening Strategies

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200116102359 ◽

2020 ◽

Vol 16 ◽

Author(s):

Pragya Nayak ◽

Monica Kachroo

Keyword(s):

Pseudomonas Aeruginosa ◽

Virtual Screening ◽

In Silico ◽

Cancer Cell Line ◽

Inhibitory Response ◽

Chemotherapeutic Agents ◽

Acceptor Site ◽

Hydrogen Bond Acceptor ◽

Screening Strategies

: A series of new heteroaryl thiazolidine-4-one derivatives were designed and subjected to in-silico prioritization using various virtual screening strategies. Two series of thiazolidinone derivatives were synthesized and screened for their in-vitro antitubercular, anticancer, antileishmanial and antibacterial (Staphylococcus aureus; Streptococcus pneumonia; Escherichia coli; Pseudomonas aeruginosa) activities. The compounds with electronegative substitutions exhibited positive antitubercular activity, the derivatives possessing a methyl substitution exhibited good inhibitory response against breast cancer cell line MCF-7 while the compounds possessing a hydrogen bond acceptor site like hydroxyl and methoxy substitution in their structures exhibited good in-vitro antileishmanial activity. Some compounds exhibited potent activity against gram positive bacteria Pseudomonas aeruginosa as compared to the standards. Altogether, the designed compounds exhibited good in-vitro anti-infective potential which was in good agreement with the in-silico predictions and they can be developed as important lead molecules for anti-infective and chemotherapeutic drug research.

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