GTPase KRas
From Proteopedia
(Difference between revisions)
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| - | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
| - | <ref>PMID:21638687</ref>. | ||
| + | <StructureSection load='4ept' size='350' side='right' caption='Structure of yeast cytosine deaminase complex with pyrimidine-based inhibitor, acetate, Ca+2 (green) and Zn+2 (grey) ions (PDB entry [[4ept]])' scene=''> | ||
== Function == | == Function == | ||
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| + | '''GTPase KRas''' (KRas) plays a critical role in the control of cellular growth. Kras stands for Kirsten rat sarcoma virus gene. KRas is a small GTPase that functions as molecular switches by alternating | ||
| + | between inactive GDP-bound state and active GTP-bound state<ref>PMID:2406906</ref>. | ||
== Disease == | == Disease == | ||
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| + | A single mutation of KRas G12C activates KRas and is implicated with various malignancies including lung adenocarcinoma, mutinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma<ref>PMID:29187496</ref>. KRas mutations are the most common genetic abnormalities in cancer. | ||
== Relevance == | == Relevance == | ||
| - | + | KRas inhibition represents an attractive therapeutic strategy for many cancers. | |
| + | == Structural highlights == | ||
| + | The GDP-bound KRas binds a small molecule inhibitor in its binding cleft following conformational change of the protein<ref>PMID:22566140</ref>. | ||
</StructureSection> | </StructureSection> | ||
== 3D Structures of GTPase KRas == | == 3D Structures of GTPase KRas == | ||
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**[[5w22]], [[4obe]], [[4lpk]], [[5vq8]] – hKRas + GDP <br /> | **[[5w22]], [[4obe]], [[4lpk]], [[5vq8]] – hKRas + GDP <br /> | ||
**[[3gft]] – hKRas (mutant) + GTP analog <br /> | **[[3gft]] – hKRas (mutant) + GTP analog <br /> | ||
| - | **[[4l8g]], [[4ldj]], [[4ql3]], [[4tq9]], [[4tqa]], [[6asa]], [[6ase]], [[5whd]], | + | **[[4l8g]], [[4ldj]], [[4ql3]], [[4tq9]], [[4tqa]], [[6asa]], [[6ase]], [[5whd]], [[5uqw]], [[5us4]], [[5vp7]], [[5vq0]], [[5vq1]], [[4wa7]], [[4lrw]] – hKRas (mutant) + GDP <br /> |
**[[5vpi]], [[5vpz]], [[5vq6]] – hKRas (mutant) + GTP <br /> | **[[5vpi]], [[5vpz]], [[5vq6]] – hKRas (mutant) + GTP <br /> | ||
**[[5usj]], [[5vpy]] – hKRas (mutant) + GNP <br /> | **[[5usj]], [[5vpy]] – hKRas (mutant) + GNP <br /> | ||
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== References == | == References == | ||
<references/> | <references/> | ||
| + | [[Category:Topic Page]] | ||
Revision as of 09:40, 25 February 2018
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3D Structures of GTPase KRas
Updated on 25-February-2018
References
- ↑ Milburn MV, Tong L, deVos AM, Brunger A, Yamaizumi Z, Nishimura S, Kim SH. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science. 1990 Feb 23;247(4945):939-45. PMID:2406906
- ↑ Shibata H, Ohike N, Norose T, Isobe T, Suzuki R, Imai H, Shiokawa A, Aoki T, Murakami M, Mizukami H, Tanaka JI, Takimoto M. Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression. Anticancer Res. 2017 Dec;37(12):7063-7068. doi: 10.21873/anticanres.12178. PMID:29187496 doi:http://dx.doi.org/10.21873/anticanres.12178
- ↑ Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW. Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation. Angew Chem Int Ed Engl. 2012 May 8. doi: 10.1002/anie.201201358. PMID:22566140 doi:10.1002/anie.201201358
