NDLI: Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic Core of Protein Kinases

Content Provider	PubMed Central
Author	Zhang, Lun Wang, Jian-chuan Hou, Li Cao, Peng-rong Wu, Li Zhang, Qian-sen Yang, Huai-yu Zang, Yi Ding, Jian-ping Jia, Li
Copyright Year	2015
Abstract	The His-x-Asp (HxD) motif is one of the most conserved structural components of the catalytic core of protein kinases; however, the functional role of the conserved histidine is unclear. Here we report that replacement of the HxD-histidine with Arginine or Phenylalanine in Aurora A abolishes both the catalytic activity and auto-phosphorylation, whereas the Histidine-to-tyrosine impairs the catalytic activity without affecting its auto-phosphorylation. Comparisons of the crystal structures of wild-type (WT) and mutant Aurora A demonstrate that the impairment of the kinase activity is accounted for by (1) disruption of the regulatory spine in the His-to-Arg mutant, and (2) change in the geometry of backbones of the Asp-Phe-Gly (DFG) motif and the DFG-1 residue in the His-to-Tyr mutant. In addition, bioinformatics analyses show that the HxD-histidine is a mutational hotspot in tumor tissues. Moreover, the H174R mutation of the HxD-histidine, in the tumor suppressor LKB1 abrogates the inhibition of anchorage-independent growth of A549 cells by WT LKB1. Based on these data, we propose that the HxD-histidine is involved in a conserved inflexible organization of the catalytic core that is required for the kinase activity. Mutation of the HxD-histidine may also be involved in the pathogenesis of some diseases including cancer.
Related Links	http://dx.doi.org/10.1038/srep10115
Starting Page	10115
File Format	PDF
ISSN	20452322
e-ISSN	20452322
Journal	Scientific Reports
Volume Number	5
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-05-11
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Science and technology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic Core of Protein Kinases

A conserved helix motif complements the protein kinase core.

His ... Asp catalytic dyad of ribonuclease A: histidine pKa values in the wild-type, D121N, and D121A enzymes.

Histidine 117 in the His-Gly-Ser-Asp motif is Required for the Biochemical Activities of Nucleoside Diphosphate Kinase of Mycobacterium smegmatis

The highly conserved amino acid sequence motif Tyr-Gly-Asp-Thr-Asp-Ser in alpha-like DNA polymerases is required by phage phi 29 DNA polymerase for protein-primed initiation and polymerization.

The role of conserved water molecules in the catalytic domain of protein kinases

Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation

Transplanting allosteric control of enzyme activity by protein–protein interactions: Coupling a regulatory site to the conserved catalytic core

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic Core of Protein Kinases

Similar Documents

Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic Core of Protein Kinases

A conserved helix motif complements the protein kinase core.

His ... Asp catalytic dyad of ribonuclease A: histidine pKa values in the wild-type, D121N, and D121A enzymes.

Histidine 117 in the His-Gly-Ser-Asp motif is Required for the Biochemical Activities of Nucleoside Diphosphate Kinase of Mycobacterium smegmatis

The highly conserved amino acid sequence motif Tyr-Gly-Asp-Thr-Asp-Ser in alpha-like DNA polymerases is required by phage phi 29 DNA polymerase for protein-primed initiation and polymerization.

The role of conserved water molecules in the catalytic domain of protein kinases

Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation

Transplanting allosteric control of enzyme activity by protein–protein interactions: Coupling a regulatory site to the conserved catalytic core

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic Core of Protein Kinases