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.


1nn1

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1nn1.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1nn1.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1nn1| PDB=1nn1 | SCENE= }}
{{STRUCTURE_1nn1| PDB=1nn1 | SCENE= }}
-
'''Crystal structure of human thymidylate kinase with ddTMP and AppNHp'''
+
===Crystal structure of human thymidylate kinase with ddTMP and AppNHp===
-
==Overview==
+
<!--
-
Nucleoside analogue prodrugs are dependent on efficient intracellular stepwise phosphorylation to their triphosphate form to become therapeutically active. In many cases it is this activation pathway that largely determines the efficacy of the drug. To gain further understanding of the determinants for efficient conversion by the enzyme thymidylate kinase (TMPK) of clinically important thymidine monophosphate analogues to the corresponding diphosphates, we solved the crystal structures of the enzyme, with either ADP or the ATP analogue AppNHp at the phosphoryl donor site, in complex with TMP, AZTMP (previous work), NH2TMP, d4TMP, ddTMP, and FLTMP (this work) at the phosphoryl acceptor site. In conjunction with steady-state kinetic data, our structures shed light on the effect of 3'-substitutions in the nucleoside monophosphate (NMP) sugar moiety on the catalytic rate. We observe a direct correlation between the rate of phosphorylation of an NMP and its ability to induce a closing of the enzyme's phosphate-binding loop (P-loop). Our results show the drastic effects that slight modifications of the substrates exert on the enzyme's conformation and, hence, activity and suggest the type of substitutions that are compatible with efficient phosphorylation by TMPK.
+
The line below this paragraph, {{ABSTRACT_PUBMED_12614151}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 12614151 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_12614151}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: P-loop]]
[[Category: P-loop]]
[[Category: Thymidylate kinase]]
[[Category: Thymidylate kinase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:44:00 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:27:39 2008''

Revision as of 02:27, 28 July 2008

Image:1nn1.png

Template:STRUCTURE 1nn1

Crystal structure of human thymidylate kinase with ddTMP and AppNHp

Template:ABSTRACT PUBMED 12614151

About this Structure

1NN1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structures of human thymidylate kinase in complex with prodrugs: implications for the structure-based design of novel compounds., Ostermann N, Segura-Pena D, Meier C, Veit T, Monnerjahn C, Konrad M, Lavie A, Biochemistry. 2003 Mar 11;42(9):2568-77. PMID:12614151

Page seeded by OCA on Mon Jul 28 05:27:39 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1nn1"
Personal tools