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.

4yvf

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:00, 12 June 2019

Structure of S-adenosyl-L-homocysteine hydrolase

Structural highlights

4yvf is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	AHCY, SAHH (HUMAN)
Activity:	Adenosylhomocysteinase, with EC number 3.3.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SAHH_HUMAN] Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:613752]. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.^[1] ^[2] ^[3] ^[4]

Function

[SAHH_HUMAN] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.^[5]

Publication Abstract from PubMed

Optimization of a new series of S-adenosyl-L-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 +/- 3, 5.0 +/- 2.0, and 8.5 +/- 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD(+) and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.

Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs.,Nakao A, Suzuki H, Ueno H, Iwasaki H, Setsuta T, Kashima A, Sunada S Bioorg Med Chem. 2015 Aug 1;23(15):4952-69. doi: 10.1016/j.bmc.2015.05.018. Epub , 2015 May 19. PMID:26037610^[6]

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

References

↑ Baric I, Fumic K, Glenn B, Cuk M, Schulze A, Finkelstein JD, James SJ, Mejaski-Bosnjak V, Pazanin L, Pogribny IP, Rados M, Sarnavka V, Scukanec-Spoljar M, Allen RH, Stabler S, Uzelac L, Vugrek O, Wagner C, Zeisel S, Mudd SH. S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4234-9. Epub 2004 Mar 15. PMID:15024124 doi:10.1073/pnas.0400658101
↑ Buist NR, Glenn B, Vugrek O, Wagner C, Stabler S, Allen RH, Pogribny I, Schulze A, Zeisel SH, Baric I, Mudd SH. S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man. J Inherit Metab Dis. 2006 Aug;29(4):538-45. Epub 2006 May 30. PMID:16736098 doi:10.1007/s10545-006-0240-0
↑ Vugrek O, Beluzic R, Nakic N, Mudd SH. S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome. Hum Mutat. 2009 Apr;30(4):E555-65. doi: 10.1002/humu.20985. PMID:19177456 doi:10.1002/humu.20985
↑ Grubbs R, Vugrek O, Deisch J, Wagner C, Stabler S, Allen R, Baric I, Rados M, Mudd SH. S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes. J Inherit Metab Dis. 2010 Dec;33(6):705-13. doi: 10.1007/s10545-010-9171-x. Epub , 2010 Sep 18. PMID:20852937 doi:10.1007/s10545-010-9171-x
↑ Yang X, Hu Y, Yin DH, Turner MA, Wang M, Borchardt RT, Howell PL, Kuczera K, Schowen RL. Catalytic strategy of S-adenosyl-L-homocysteine hydrolase: transition-state stabilization and the avoidance of abortive reactions. Biochemistry. 2003 Feb 25;42(7):1900-9. PMID:12590576 doi:http://dx.doi.org/10.1021/bi0262350
↑ Nakao A, Suzuki H, Ueno H, Iwasaki H, Setsuta T, Kashima A, Sunada S. Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs. Bioorg Med Chem. 2015 Aug 1;23(15):4952-69. doi: 10.1016/j.bmc.2015.05.018. Epub , 2015 May 19. PMID:26037610 doi:http://dx.doi.org/10.1016/j.bmc.2015.05.018

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yvf"

@@ Line 1: / Line 1: @@
 ==Structure of S-adenosyl-L-homocysteine hydrolase==
-<StructureSection load='4yvf' size='340' side='right' caption='[[4yvf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='4yvf' size='340' side='right'caption='[[4yvf]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yvf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yvf]] is a 2 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=4YVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=XFA:2-{[5-CHLORO-2-(4-CHLOROPHENOXY)PHENYL](2-{[2-(METHYLAMINO)ETHYL]AMINO}-2-OXOETHYL)AMINO}-N-(1,3-DIHYDRO-2H-ISOINDOL-2-YL)-N-METHYLACETAMIDE'>XFA</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AHCY, SAHH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylhomocysteinase Adenosylhomocysteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.1.1 3.3.1.1] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yvf OCA], [http://pdbe.org/4yvf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yvf RCSB], [http://www.ebi.ac.uk/pdbsum/4yvf PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yvf OCA], [http://pdbe.org/4yvf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yvf RCSB], [http://www.ebi.ac.uk/pdbsum/4yvf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yvf ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[Category: Adenosylhomocysteinase]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Akiko, K]]
 [[Category: Hydrolase]]
 [[Category: Sahh]]

4yvf

From Proteopedia

Revision as of 07:00, 12 June 2019

Structure of S-adenosyl-L-homocysteine hydrolase

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox