1k7d: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
Line 1: Line 1:
[[Image:1k7d.gif|left|200px]]
{{Seed}}
[[Image:1k7d.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1k7d|  PDB=1k7d  |  SCENE=  }}  
{{STRUCTURE_1k7d|  PDB=1k7d  |  SCENE=  }}  


'''Penicillin Acylase mutant with Phenyl Proprionic Acid'''
===Penicillin Acylase mutant with Phenyl Proprionic Acid===




==Overview==
<!--  
Penicillin acylase catalyses the condensation of Calpha-substituted phenylacetic acids with beta-lactam nucleophiles, producing semi-synthetic beta-lactam antibiotics. For efficient synthesis a low affinity for phenylacetic acid and a high affinity for Calpha-substituted phenylacetic acid derivatives is desirable. We made three active site mutants, alphaF146Y, betaF24A and alphaF146Y/betaF24A, which all had a 2- to 10-fold higher affinity for Calpha-substituted compounds than wild-type enzyme. In addition, betaF24A had a 20-fold reduced affinity for phenylacetic acid. The molecular basis of the improved properties was investigated by X-ray crystallography. These studies showed that the higher affinity of alphaF146Y for (R)-alpha-methylphenylacetic acid can be explained by van der Waals interactions between alphaY146:OH and the Calpha-substituent. The betaF24A mutation causes an opening of the phenylacetic acid binding site. Only (R)-alpha-methylphenylacetic acid, but not phenylacetic acid, induces a conformation with the ligand tightly bound, explaining the weak binding of phenylacetic acid. A comparison of the betaF24A structure with other open conformations of penicillin acylase showed that betaF24 has a fixed position, whereas alphaF146 acts as a flexible lid on the binding site and reorients its position to achieve optimal substrate binding.
The line below this paragraph, {{ABSTRACT_PUBMED_15254299}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 15254299 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_15254299}}


==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Ntn-hydrolase fold]]
[[Category: Ntn-hydrolase fold]]
[[Category: Phenyl proprionic acid]]
[[Category: Phenyl proprionic acid]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:23:59 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 09:54:00 2008''

Revision as of 06:54, 2 July 2008

File:1k7d.png

Template:STRUCTURE 1k7d

Penicillin Acylase mutant with Phenyl Proprionic Acid

Template:ABSTRACT PUBMED 15254299

About this Structure

1K7D is a Protein complex structure of sequences from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Structural and kinetic studies on ligand binding in wild-type and active-site mutants of penicillin acylase., Alkema WB, Hensgens CM, Snijder HJ, Keizer E, Dijkstra BW, Janssen DB, Protein Eng Des Sel. 2004 May;17(5):473-80. Epub 2004 Jul 14. PMID:15254299

Page seeded by OCA on Wed Jul 2 09:54:00 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=1k7d&oldid=619495"