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.


1d5b

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1d5b.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1d5b.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1d5b| PDB=1d5b | SCENE= }}
{{STRUCTURE_1d5b| PDB=1d5b | SCENE= }}
-
'''UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY'''
+
===UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY===
-
==Overview==
+
<!--
-
Antibody AZ-28 was generated against the chairlike transition-state analogue (TSA) 1 and catalyzes the oxy-Cope rearrangement of substrate 2 to product 3. The germline precursor to AZ-28 catalyzes the reaction with a 35-fold higher rate (k(cat)/k(uncat) = 163 000), despite a 40-fold lower binding affinity for TSA.1 (K(D) = 670 nM). To determine the structural basis for the differences in the binding and catalytic properties of the germline and affinity-matured antibodies, the X-ray crystal structures of the unliganded and TSA.1 complex of antibody AZ-28 have been determined at 2.8 and 2.6 A resolution, respectively; the structures of the unliganded and TSA.1 complex of the germline precursor to AZ-28 were both determined at 2. 0 A resolution. In the affinity-matured antibody.hapten complex the TSA is fixed in a catalytically unfavorable conformation by a combination of van der Waals and hydrogen-bonding interactions. The 2- and 5-phenyl substituents of TSA.1 are almost perpendicular to the cyclohexyl ring, leading to decreased orbital overlap and decreased stabilization of the putative transition state. The active site of the germline antibody appears to have an increased degree of flexibility-CDRH3 moves 4.9 A outward from the active site upon binding of TSA.1. We suggest that this conformational flexibility in the germline antibody, which results in a lower binding affinity for TSA.1, allows dynamic changes in the dihedral angle of the 2-phenyl substituent along the reaction coordinate. These conformational changes in turn lead to enhanced orbital overlap and increased catalytic rate. These studies suggest that protein and substrate dynamics play a key role in this antibody-catalyzed reaction.
+
The line below this paragraph, {{ABSTRACT_PUBMED_10651626}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 10651626 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_10651626}}
==About this Structure==
==About this Structure==
Line 27: Line 31:
[[Category: Stevens, R C.]]
[[Category: Stevens, R C.]]
[[Category: Immune system]]
[[Category: Immune system]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:28:01 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 22:26:23 2008''

Revision as of 19:26, 30 June 2008

Image:1d5b.png

Template:STRUCTURE 1d5b

UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY

Template:ABSTRACT PUBMED 10651626

About this Structure

1D5B is a Protein complex structure of sequences from Mus musculus and homo sapiens. Full crystallographic information is available from OCA.

Reference

Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement., Mundorff EC, Hanson MA, Varvak A, Ulrich H, Schultz PG, Stevens RC, Biochemistry. 2000 Feb 1;39(4):627-32. PMID:10651626

Page seeded by OCA on Mon Jun 30 22:26:23 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1d5b"
Personal tools