Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

G Zimmermann, B Papke, S Ismail, N Vartak… - Nature, 2013 - nature.com
The KRAS oncogene product is considered a major target in anticancer drug discovery 1, 2,
3. However, direct interference with KRAS signalling has not yet led to clinically useful drugs
3, 4, 5, 6, 7, 8. Correct localization and signalling by farnesylated KRAS is regulated by the …

The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins

…, D Perera, L Cassidy, F Skoulidis, SA Ismail… - Nature cell …, 2012 - nature.com
We identify a role for the GDI-like solubilizing factor (GSF) PDEδ in modulating signalling
through Ras family G proteins by sustaining their dynamic distribution in cellular
membranes. We show that the GDI-like pocket of PDEδ binds and solubilizes farnesylated …

Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo

SA Ismail, YX Chen, A Rusinova, A Chandra… - Nature chemical …, 2011 - nature.com
Abstract Lipidated Rho and Rab GTP-binding proteins are transported between membranes
in complex with solubilizing factors called'guanine nucleotide dissociation inhibitors'(GDIs).
Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but …

Post‐proteomic identification of a novel phage‐encoded streptodornase, Sda1, in invasive M1T1 Streptococcus pyogenes

RK Aziz, SA Ismail, HW Park, M Kotb - Molecular microbiology, 2004 - Wiley Online Library
The M1T1 strain remains the most frequently isolated strain from group A streptococcal
(GAS) infection cases worldwide. We previously reported that M1T1 differs from the fully
sequenced M1 SF370 strain. To better understand the reason for the persistence and …

Structural basis for Arl3‐specific release of myristoylated ciliary cargo from UNC119

SA Ismail, YX Chen, M Miertzschke… - The EMBO …, 2012 - emboj.embopress.org
Access to the ciliary membrane for trans‐membrane or membrane‐associated proteins is a
regulated process. Previously, we have shown that the closely homologous small G proteins
Arl2 and Arl3 allosterically regulate prenylated cargo release from PDEδ. UNC119/HRG4 is …

[HTML][HTML] The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism

SA Ismail, IR Vetter, B Sot, A Wittinghofer - Cell, 2010 - Elsevier
Arfs are small G proteins that have a key role in vesicle trafficking and cytoskeletal
remodeling. ArfGAP proteins stimulate Arf intrinsic GTP hydrolysis by a mechanism that is
still unresolved. Using a fusion construct we solved the structure of the ArfGAP ASAP3 in …

Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3‐effector‐GAP complex

S Veltel, A Kravchenko, S Ismail, A Wittinghofer - FEBS letters, 2008 - Wiley Online Library
MINT‐6602303: ARL2 (uniprotkb: P36404) binds (MI: 0407) to HRG4 (uniprotkb: Q13432)
by pull down (MI: 0096) MINT‐6602333: ARL3 (uniprotkb: P36405) binds (MI: 0407) to CoD
(uniprotkb: Q9BTW9) by pull down (MI: 0096) MINT‐6602347, MINT‐6602369: RP2 …

[HTML][HTML] Identification of pyrazolopyridazinones as PDEδ inhibitors

…, M Kovacevic, DC Truxius, EK Fansa, S Ismail… - Nature …, 2016 - nature.com
The prenyl-binding protein PDEδ is crucial for the plasma membrane localization of
prenylated Ras. Recently, we have reported that the small-molecule Deltarasin binds to the
prenyl-binding pocket of PDEδ, and impairs Ras enrichment at the plasma membrane …

The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo

…, YX Chen, A Wittinghofer, S Ismail - EMBO …, 2013 - embor.embopress.org
Defects in primary cilia result in human diseases known as ciliopathies. The retinitis
pigmentosa GTPase regulator (RPGR), mutated in the most severe form of the eye disease,
is located at the transition zone of the ciliary organelle. The RPGR‐interacting partner PDEδ …

Structural analysis of human liver glyceraldehyde-3-phosphate dehydrogenase

SA Ismail, HW Park - Acta Crystallographica Section D: Biological …, 2005 - scripts.iucr.org
The crystal structure of human liver glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
has been determined. This structure represents the first moderate-resolution (2.5 Å) and
crystallographically refined (Rfree= 22.9%) human GAPDH structure. The liver GAPDH …