| Title | Crystal structure of Homoserine dehydrogenase (NP_394635.1) from THERMOPLASMA ACIDOPHILUM at 1.95 A resolution. | | Site | JCSG | | PDB Id | | Target Id | 380082 | | Molecular Characteristics | | Source | Thermoplasma acidophilum | | Alias Ids | NP_394635.1 | Molecular Weight | 35603.14 Da. | | Residues | 324 | Isoelectric Point | 5.44 | | Sequence | mkeiriilmgtgnvglnvlriidasnrrrsafsikvvgvsdsrsyasgrnldissiisnkektgrisdra fsgpedlmgeaadllvdctpasrdgvreyslyrmafesgmnvvtanksglankwhdimdsanqnskyir yeatvaggvplfsvldysilpskvkrfrgivsstinyvirnmangrslrdvvddaikkgiaesnpqddl ngldaarksvilvnhifgteytlndveysgvdersynandrlvtevyvddrrpvavsriislnkddflm sigmdglgyqietdsngtvnvsdiydgpyetagavvndilllskvqk | | | BLAST FFAS |
| Structure Determination | | Method | XRAY | Chains | 1 | | Resolution (Å) | 1.95 | Rfree | 0.193 | | Matthews' coefficent | 2.69 | Rfactor | 0.152 | | Waters | 215 | Solvent Content | 54.24 |
| Ligand Information | | Ligands | NDP (NADPH) x 1;EDO (1,2-ETHANEDIOL) x 6 | | Metals | NA (SODIUM) x 1 | |  | /content/body/table/tbody/tr/td[2]/center/table/tbody/tr[2]/td/center/span, reference to undefined name 'jmol': line 1, column 1 (click for details)MindTouch.Deki.Script.DekiScriptUndefinedNameException: reference to undefined name 'jmol': line 1, column 1
at MindTouch.Deki.Script.DekiScriptVar.Evaluate (MindTouch.Deki.Script.DekiScriptEnv env) [0x00000]
at MindTouch.Deki.Script.DekiScriptAccess.Evaluate (MindTouch.Deki.Script.DekiScriptEnv env, Boolean evaluateProperties) [0x00000]
at MindTouch.Deki.Script.DekiScriptAccess.Evaluate (MindTouch.Deki.Script.DekiScriptEnv env) [0x00000]
at MindTouch.Deki.Script.DekiScriptCall.Evaluate (MindTouch.Deki.Script.DekiScriptEnv env) [0x00000]
at MindTouch.Deki.Script.Dom.DekiScriptDomExpr.Evaluate (MindTouch.Deki.Script.DekiScriptEvalContext context, System.Xml.XmlNode parent, MindTouch.Deki.Script.DekiScriptEnv env) [0x00000] | |
| /content/body/table/tbody/tr/td[2]/center/table/tbody/tr[6]/td/center/table/tbody/tr/td/span, function 'template' failed (click for details)MindTouch.Deki.Script.DekiScriptInvokeException: function 'template' failed ---> System.ArgumentException: could not convert parameter 'target' (index 2) from list to str
at MindTouch.Deki.DekiScriptFunction+DekiScriptInvokeDelegateWrapper.Invoke (MindTouch.Deki.Script.DekiScriptLiteral arguments) [0x00000]
at MindTouch.Deki.DekiExtNativeFunction.Invoke (MindTouch.Deki.Script.DekiScriptLiteral arguments) [0x00000]
at MindTouch.Deki.Script.DekiScriptRuntime+<Invoke>d__0.MoveNext () [0x00000]
--- End of inner exception stack trace ---
at MindTouch.Deki.Script.DekiScriptRuntime+<Invoke>d__0.MoveNext () [0x00000]
at MindTouch.Tasking.Coroutine.Invoke (System.Func`1 invocation) [0x00000]
--- End of exception stack trace ---
at MindTouch.Deki.Script.DekiScriptRuntime.Invoke(XUri uri, DekiScriptLiteral args, DekiScriptEnv env, Result`1 result)
at MindTouch.Deki.Script.DekiScriptRuntime.Invoke(XUri uri, DekiScriptLiteral args, DekiScriptEnv env, Result`1 result)
at MindTouch.Deki.DekiWikiService.GetPageContents(DreamContext context, DreamMessage request, Result`1 response)
--- End of coroutine stack trace --- | | |
Protein Summary
Gene NP_394635.1 from Thermoplasma Acidophilum encodes a protein with 324 residues consisting of two domains, N-terminal domian (2-118) and C-terminal Domain(119-324). This target has been annotated homoserine dehydrogenase related protein initially. FFAS and SSM suggest this target is a structural homolog mainly to homoserine dehydrogenase (PDB ID: 1Q7G, 1EBF) with conserved residues in the active site. One NAD(P)H from bacteria natural processing is found and modeled in the conserved active site, consisting of K117, glu201, Asp 207 and Asp 212. One Ca2+ is also modeled in the structure. The interface interaction indicates that the biomolecule of protein NP_394635.1 should be a dimer.
Figure 1. Protein NP_394635.1 monomer has a conserved active site in N-terminal near
the interface between N-terminal and C-terminal. One NAD(P)H is modeled in the structure.
Figure 2. The biomolecule of NP_394635.1 is a dimer.
Figure 3. Protein NP_394635.1 (green) is a structural homolog to 1Q7G(Blue), 1EBF(Magenta)
and JCSG target 3DO5(Yellow).
Figure 4. The binding of NAD(P)H in the conserved active sited indicates a big movement of the loop(green, residue 195~206), which is not seen its structural homologus.
References,
1. DeLaBarre, B., Thompson, P.R., Wright, G.D., Berghuis, A.M. (2000) Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases. Nat.Struct.Biol. 7: 238-244
2. Jacques, S.L., Mirza, I.A., Ejim, L., Koteva, K., Hughes, D.W., Green, K., Kinach, R., Honek, J.F., Lai, H.K., Berghuis, A.M., Wright, G.D. (2003) Enzyme assisted suicide: Molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase Chem.Biol. 10: 989-995
Ligand Summary
