This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1b55

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1b55.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1b55.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1b55| PDB=1b55 | SCENE= }}
{{STRUCTURE_1b55| PDB=1b55 | SCENE= }}
-
'''PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE'''
+
===PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE===
-
==Overview==
+
<!--
-
BACKGROUND: The activity of Bruton's tyrosine kinase (Btk) is important for the maturation of B cells. A variety of point mutations in this enzyme result in a severe human immunodeficiency known as X-linked agammaglobulinemia (XLA). Btk contains a pleckstrin-homology (PH) domain that specifically binds phosphatidylinositol 3,4,5-trisphosphate and, hence, responds to signalling via phosphatidylinositol 3-kinase. Point mutations in the PH domain might abolish membrane binding, preventing signalling via Btk. RESULTS: We have determined the crystal structures of the wild-type PH domain and a gain-of-function mutant E41K in complex with D-myo-inositol 1,3,4,5-tetra-kisphosphate (Ins (1,3,4,5)P4). The inositol Ins (1,3,4,5)P4 binds to a site that is similar to the inositol 1,4,5-trisphosphate binding site in the PH domain of phospholipase C-delta. A second Ins (1,3,4,5)P4 molecule is associated with the domain of the E41K mutant, suggesting a mechanism for its constitutive interaction with membrane. The affinities of Ins (1,3,4,5)P4 to the wild type (Kd = 40 nM), and several XLA-causing mutants have been measured using isothermal titration calorimetry. CONCLUSIONS: Our data provide an explanation for the specificity and high affinity of the interaction with phosphatidylinositol 3,4,5-trisphosphate and lead to a classification of the XLA mutations that reside in the Btk PH domain. Mis-sense mutations that do not simply destabilize the PH fold either directly affect the interaction with the phosphates of the lipid head group or change electrostatic properties of the lipid-binding site. One point mutation (Q127H) cannot be explained by these facts, suggesting that the PH domain of Btk carries an additional function such as interaction with a Galpha protein.
+
The line below this paragraph, {{ABSTRACT_PUBMED_10196129}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 10196129 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_10196129}}
==About this Structure==
==About this Structure==
Line 39: Line 43:
[[Category: X-linked agammaglobulinemia]]
[[Category: X-linked agammaglobulinemia]]
[[Category: Zinc binding]]
[[Category: Zinc binding]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:05:08 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:17:27 2008''

Revision as of 15:17, 30 June 2008

Image:1b55.png

Template:STRUCTURE 1b55

PH DOMAIN FROM BRUTON'S TYROSINE KINASE IN COMPLEX WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE

Template:ABSTRACT PUBMED 10196129

About this Structure

1B55 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate., Baraldi E, Djinovic Carugo K, Hyvonen M, Surdo PL, Riley AM, Potter BV, O'Brien R, Ladbury JE, Saraste M, Structure. 1999 Apr 15;7(4):449-60. PMID:10196129

Page seeded by OCA on Mon Jun 30 18:17:27 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1b55"
Personal tools