1bx4

From Proteopedia

(Difference between revisions)

Revision as of 07:06, 10 October 2019

STRUCTURE OF HUMAN ADENOSINE KINASE AT 1.50 ANGSTROMS

Structural highlights

1bx4 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	Adenosine kinase, with EC number 2.7.1.20
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ADK_HUMAN] Defects in ADK are the cause of hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:614300]. A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.^[1]

Function

[ADK_HUMAN] ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Adenosine kinase (AK) is a key enzyme in the regulation of extracellular adenosine and intracellular adenylate levels. Inhibitors of adenosine kinase elevate adenosine to levels that activate nearby adenosine receptors and produce a wide variety of therapeutically beneficial activities. Accordingly, AK is a promising target for new analgesic, neuroprotective, and cardioprotective agents. We determined the structure of human adenosine kinase by X-ray crystallography using MAD phasing techniques and refined the structure to 1.5 A resolution. The enzyme structure consisted of one large alpha/beta domain with nine beta-strands, eight alpha-helices, and one small alpha/beta-domain with five beta-strands and two alpha-helices. The active site is formed along the edge of the beta-sheet in the large domain while the small domain acts as a lid to cover the upper face of the active site. The overall structure is similar to the recently reported structure of ribokinase from Escherichia coli [Sigrell et al. (1998) Structure 6, 183-193]. The structure of ribokinase was determined at 1.8 A resolution and represents the first structure of a new family of carbohydrate kinases. Two molecules of adenosine were present in the AK crystal structure with one adenosine molecule located in a site that matches the ribose site in ribokinase and probably represents the substrate-binding site. The second adenosine site overlaps the ADP site in ribokinase and probably represents the ATP site. A Mg2+ ion binding site is observed in a trough between the two adenosine sites. The structure of the active site is consistent with the observed substrate specificity. The active-site model suggests that Asp300 is an important catalytic residue involved in the deprotonation of the 5'-hydroxyl during the phosphate transfer.

Structure of human adenosine kinase at 1.5 A resolution.,Mathews II, Erion MD, Ealick SE Biochemistry. 1998 Nov 10;37(45):15607-20. PMID:9843365^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bjursell MK, Blom HJ, Cayuela JA, Engvall ML, Lesko N, Balasubramaniam S, Brandberg G, Halldin M, Falkenberg M, Jakobs C, Smith D, Struys E, von Dobeln U, Gustafsson CM, Lundeberg J, Wedell A. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am J Hum Genet. 2011 Oct 7;89(4):507-15. doi: 10.1016/j.ajhg.2011.09.004. Epub, 2011 Sep 28. PMID:21963049 doi:10.1016/j.ajhg.2011.09.004
↑ Mathews II, Erion MD, Ealick SE. Structure of human adenosine kinase at 1.5 A resolution. Biochemistry. 1998 Nov 10;37(45):15607-20. PMID:9843365 doi:10.1021/bi9815445

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bx4"

@@ Line 1: / Line 1: @@
 ==STRUCTURE OF HUMAN ADENOSINE KINASE AT 1.50 ANGSTROMS==
-<StructureSection load='1bx4' size='340' side='right' caption='[[1bx4]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+<StructureSection load='1bx4' size='340' side='right'caption='[[1bx4]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1bx4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BX4 FirstGlance]. <br>
@@ Line 16: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bx/1bx4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bx/1bx4_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1bx4" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Adenosine kinase|Adenosine kinase]]
+*[[Adenosine kinase 3D structures|Adenosine kinase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 41: @@
 [[Category: Adenosine kinase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ealick, S E]]
 [[Category: Erion, M D]]

1bx4

From Proteopedia

Revision as of 07:06, 10 October 2019

STRUCTURE OF HUMAN ADENOSINE KINASE AT 1.50 ANGSTROMS

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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